Following the

introduction of a new programme of vaccinat

Following the

introduction of a new programme of vaccination, the incidence of infection would be expected to follow a well recognised pattern [48] and [49]. There is an initial drop in incidence, called the honeymoon period, brought about by the addition of protection arising from immunisation to the existing naturally acquired check details immunity. The resulting fall in incidence leads to a reduction in naturally acquired immunity, allowing a partial rebound. Infection incidence then settles into a new suppressed cycle. This pattern is consistent with the observed pattern of laboratory confirmed influenza in England and Wales. While the temporal pattern of influenza incidence is consistent with the available observed data, the lack of recent population wide data on infection incidence and prevalence is a PFI-2 purchase limitation to modelling influenza transmission. The collection of good quality population level data on the incidence and prevalence of influenza infection would help to reduce uncertainty when calibrating such models. However, alternative analyses of the impact of vaccination policies, which fail to account for the dynamic nature of transmission, risk seriously underestimating the potential effects of such policies. A further weakness in the

model is the inconclusive Amisulpride nature of data on the duration of vaccine induced immunity as well as on that arising from natural infection. Should the duration of vaccine induced immunity be significantly shorter than its naturally arising counterpart, then the impact of paediatric vaccination would be reduced. While multiple studies have shown the indirect benefit (herd immunity) in adults through vaccinating children against influenza [41], [50] and [51], each of these studies used different study designs resulting in variability in the estimated benefits. Additional studies comparing

real world dynamics of influenza transmission against dynamic models are of interest. This analysis demonstrates the complex and inter-related nature of factors influencing the evaluation of paediatric influenza vaccination. While there remains uncertainty in many of the parameters, the qualitative picture emerging suggests that paediatric vaccination may result in substantial benefits to children, as well as to those at risk of influenza related complications and to the elderly. “
“Dengue fever is a common mosquito-borne viral disease that represents a major worldwide public health concern, particularly for those living in tropical countries and people traveling to these zones. Globally, more than 2.5 billion people are exposed to dengue virus (DENV) infection in endemic areas, and thousands of them die each year [1].

Briefly, OMVs from serogroup B meningococci were adsorbed to fluo

Briefly, OMVs from serogroup B meningococci were adsorbed to fluorescent polystyrene latex microspheres (Fluoresbrite Plain Microspheres, Polysciences, Warrington, Pennsylvania) of approximately size of meningococci (1 μm of diameter). FITC was incorporated within the polymer, leaving the surface free to adsorb

the protein. The latex beads (500 μl, 4.55 × 1010 beads/ml) ATM Kinase Inhibitor ic50 were centrifuged at 15,600 × g for 5 min, and the pellet was suspended in a 940 μg/ml solution of OMV in 0.1 M borate buffer (0.1 M boric acid, adjusted to pH 8.5) followed by end-to-end rotation overnight (20 h) at 20 °C. After additional blocking of unreacted sites on the OMV beads with 2% bovine serum albumin (BSA) in 0.1 M borate buffer, the OMV-bead pellet was suspended in storage buffer (0.1 M phosphate buffer, containing 5% glycerol, 0.02% merthiolate and 1% BSA, pH 7.4), and kept protected from daylight in aliquots

at 4 °C until used. The antigen coated bead suspensions (100 μl, 3.3 × 108 beads/ml) were opsonised for 8 min with 25 μl of diluted test serum (1:20) previously heat inactivated at 56 °C for 30 min, with a total sample volume of 400 μl obtained by addition of PBS–BSA, supplemented with CaCl2 (0.98 mM) and MgCl2 (1 mM). 25 μl of human serum that lacked detectable intrinsic opsonisation activity diluted at 1% was added to the reaction and were incubated with end-to-end rotation for 8 min at 37 °C. Donor leukocytes (100 μl, 1.25 × 107/ml) were added and the suspensions Idoxuridine were incubated for 8 min. Phagocytosis was terminated by adding 1.5 ml of ice-cold PBS supplemented with 0.02% EDTA. The suspensions were kept on ice until analyzed PI3K inhibitor by a FACScalibur flow cytometer [16]. The levels of significance of the differences between groups were examined by Paired or Unpaired t test (parametric tests) For nonparametric data we used Mann–Whitney test (unpaired samples) or Wilcoxon matched pair test (paired samples). These analyses were performed with a GraphPad-Prism software, version 4.02. P < 0.05 was taken as significant. Fig. 1A shows the percent of specific

memory B-cells detected as specific ASC after in vitro stimulation of peripheral blood memory B-cells for 6 days. Memory B-cells were detected only in one individual 7 days after the first dose (0.5%) and in 2 individuals at 14 days (mean of 0.16%). A significant memory B-cell response was seen 7 days (mean of 0.27%) and 14 days (mean of 0.46%) after the third vaccination. At this time, memory B-cells were detected in all individuals, with frequencies varying from 0.14 to 0.95%. A significant decrease of memory B-cells was recorded 6 months (mean of 0.03%) later (pre-booster). Surprisingly, 14 days after the booster dose, only 2 of 5 individuals responded with an increase in memory B-cell frequencies with values of 0.15% and 0.34% (mean of 0.1% for all individuals). As can be seen in Fig. 1B, we observed a continuous and gradual decrease (P > 0.

Unlike LAC, the selected school districts in SCC are small and pr

Unlike LAC, the selected school districts in SCC are small and preferred not to be identified by name. Thus, in the analysis they are labeled as District A, B, C, and D. The SCC protocol was reviewed and approved by the Ann and Robert H. Lurie

Children’s Hospital of Chicago Research Center Institutional Review Board. All LAUSD schools in LAC and all schools in the four selected school districts in SCC were included in the comparison described for the school years (SY) 2010–11 to 2011–2012. To compare the changes in nutrient levels after implementation of the nutrition interventions in both counties, we used the October 2010 school breakfast and lunch menus for elementary Wnt inhibitor review and secondary schools in LAUSD and compared them to the October 2011 menus. For SCC, we used the May–June 2011 (three consecutive weeks) school breakfast and lunch menus for elementary schools and compared them to the March–May 2012 (three consecutive weeks) menus. These comparison time points were chosen based on the timeline of intervention implementation in each county, accounting for lag time between the two locales, but preserving the pre- and post-intervention interval at approximately 12 months apart. The post intervention results were then examined to see if they aligned with the IOM (for LAUSD) and Alliance for a Healthier find more Generation (for SCC) school

meal recommendations. Both counties had data for the following nutrients: food energy (kcal), protein (grams “g”), fiber (g), total fat (g), saturated fat (g), sugar (g), and sodium (milligrams “mg”). Means, 95% CIs, and percent change of nutrient

levels pre- and post-intervention were compared for all LAUSD schools and all schools in the four districts in SCC. T-tests were performed to determine if nutrient changes were significant; where appropriate, log transformations were employed. Participation frequency (i.e., the number of students participating in school breakfast and lunch), average change in kilocalories per meal for breakfast and lunch, and the number of serving days per year were calculated and used to estimate net calories (kcal) offered annually for full-time (5 days per week) meal program participants (per student per year). Nutrition Electron transport chain interventions implemented by LAUSD, which were based on IOM recommendations for healthy school meals (IOM, 2009), resulted in significant reductions in mean caloric and mean sugar content of breakfast and lunch school meals (Table 3). Similarly, for most meal categories, mean sodium content dropped. The most dramatic reductions were observed in the breakfast category for mean sugar, mean total fat, and mean sodium content. Although protein increased in the lunch meal category for elementary schools, the nutrient decreased in all other meal categories. Dietary fiber also decreased in all meal categories.

20, 95% CI 0 06 to 0 33, n = 661) were poorly and positively corr

20, 95% CI 0.06 to 0.33, n = 661) were poorly and positively correlated. Partnership building is the use of partnership statements, paraphrasing, and requests for patient’s opinion (Hall et al 1994). Interestingly, giving information to educate patients had a fair, positive correlation with satisfaction with consultation (pooled r = 0.28, 95% CI 0.04 to 0.48, n = 281), however, findings from individual studies were inconsistent for similar constructs, with r values ranging from –0.02 to 0.20 (Table 3). Individual studies

found fair to moderate correlations between verbal communication factors and satisfaction. The strongest associations were observed for use of negative questions (r = 0.30) to gather information; language reciprocity (r = 0.48) and expressions of uncertainty (r = 0.40) as facilitators; expressions of support and sympathy (r ranging from 0.19 to 0.58); listening (r = 0.27) and engaging (r = 0.22) to involve patients. LY2835219 in vitro They were reported to have a positive correlation with satisfaction with consultation (Table 3). Language reciprocity is the use of similar words by both the BMS 354825 patient and the clinician (Rowland-Morin and Carroll 1990), and expression of uncertainty is the direct and unambiguous expression of uncertainty (eg, use of the expression ‘I don’t know’) (Gordon et al

2000). Use of psychosocial questions (r = –0.15, 95% CI –0.29 to 0.00) and use of social niceties such as the expression ‘Thank you’ (r = 0.15, 95% CI –0.07 to 0.36) were not correlated with satisfaction with the consultation. Nonverbal factors: Pooled analysis was possible for four nonverbal factors employed by clinicians reported in seven studies (Bensing 1991, Comstock et al 1982, Greene et al 1994, Hunfeld et al 1999, Mead et al 2002, Smith et al 1981, Street and Buller 1987) (Figure 3). The nonverbal factors of length of consultation (pooled r = 0.30, 95% CI 0.08 to 0.49, n = 260) and nonverbal caring expressions of support (pooled r = 0.24, 95% CI 0.10 to 0.36, n = 197) had a fair, positive correlation with satisfaction with consultation. Showing interest as a facilitator

had a fair, positive correlation (pooled r = 0.23, 95% CI 0.05 to 0.39, crotamiton n = 127). Individual studies showed that the strongest associations were reported for discussing prevention (r = 0.53) (Smith et al 1981) and ability to decode body language, defined as the ability to understand patients’ nonverbal body language expressions except facial expression (r = 0.36) (DiMatteo et al 1979, Dimatteo and Taranta 1979, DiMatteo et al 1980). Positive associations were also found for ability to decode (r = 0.16) and encode (r = 0.30) tone of voice (DiMatteo et al 1979, Dimatteo and Taranta 1979, DiMatteo et al 1980) and shared laughter (r = 0.34) (Greene et al 1994) to facilitate and involve patients (Table 4). Use of nonverbal factors that appeared to avoid negative communication (r =-0.


“Although

the majority of individuals achieve an i


“Although

the majority of individuals achieve an independent gait after stroke, many do not reach a walking level that enables them to perform all their daily activities (Flansbjer et al 2005). Typically, the mean walking speed for the majority of community-dwelling people after stroke ranges from 0.4 m/s to 0.8 m/s (Duncan et al 1998, Eng et al 2002, Green et al 2002, Pohl et al 2002, Ada et al 2003). This slow speed frequently prevents their full participation in community activities. Additionally, people report a lack of ability Temozolomide cost to cover long distances after stroke, restricting their participation in work and social activities (Combs et al 2012). Moreover, walking ability has been found Ruxolitinib order to be related to community

participation (Robinson 2011). While the goal of inpatient rehabilitation is independent and safe ambulation, once individuals return home, rehabilitation aims to enhance community ambulation skills by increasing walking speed and endurance. Lord et al (2004) found that the ability to confidently negotiate uneven terrain, private venues, malls and other public venues is the most relevant predictor of community ambulation. Therefore, in order to enhance community participation, rehabilitation has focused on identifying the best approach to optimise walking speed and walking distance. One approach to improving gait is the use of mechanically assisted walking devices, such as treadmills or gait trainers. Two Cochrane systematic reviews have examined

these devices separately: Moseley et al (2005) reported on treadmill training and Mehrholz (2010) examined electromechanically-assisted training. We wanted to examine all devices that will help improve walking in the one review. In ambulatory stroke, mechanically assisted walking, whether by treadmills or gait trainers, allows an intensive amount of stepping practice by working as a ‘forced use’. Mechanically assisted walking also facilitates the practice of a more normal walking pattern because it forces appropriate timing between lower limbs, promotes hip extension during the stance phase of walking and discourages common compensatory behaviours Cell press such as circumduction (Harris-Love et al 2001, Ada et al 2003, Moore et al 2010). We have already taken this approach in What is already known on this topic: Mechanically assisted walking training, which can involve interventions such as treadmill training or electromechanical gait trainers, increases independent walking among people who have been unable to walk after stroke. However, previous systematic reviews have not drawn clear conclusions about the effect of treadmill training or gait trainers among ambulatory stroke survivors specifically. What this study adds: Compared with no intervention or with an intervention with no walking training component, treadmill training improved walking speed and distance among ambulatory people after stroke.

CD57 est également capable de médier des interactions cellulaires

CD57 est également capable de médier des interactions cellulaires homotypiques avec des glycolipides. Ainsi, à travers ses fonctions de molécule d’adhésion, CD57 participe à des phénomènes

de migration cellulaire faisant intervenir des interactions cellule-cellule et cellule-matrice extracellulaire. Elle intervient également dans le processus de réinnervation des muscles par les motoneurones [5]. Son niveau d’expression en surface est stable entre les clonotypes T CD8+ et ce, quel que Regorafenib in vitro soit leur niveau de maturation [6]. La population de lymphocytes T CD8+/CD57+ inclut des lymphocytes T cytotoxiques ainsi que des lymphocytes T régulateurs. La molécule CD57 ne semble pas jouer un rôle LY294002 ic50 direct dans ces fonctions. Les lymphocytes T CD8+/CD57+ doués de propriétés cytotoxiques expriment les marqueurs de cytotoxicité classiques comme la perforine, les granzymes A et B et la granulysine. Après stimulation avec un anticorps anti-CD3, ils sont capables de libérer ces substances

cytolytiques ; et de produire de grandes quantités de cytokines comme de l’interféron-γ et du tumor necrosis factor (TNF)-α [7]. Ces lymphocytes sont également capables de sécréter de l’interleukine-5. Ils ont été ainsi été impliqués dans la survenue d’un tableau d’asthme chez certains patients [8]. Fossariinae Les lymphocytes T CD8+/CD57+ peuvent également être régulateurs. Le surnageant des lymphocytes T CD8+/CD57+ est ainsi capable d’inhiber l’activation polyclonale et les fonctions cytotoxiques des lymphocytes T ainsi que la production d’immunoglobulines chez l’individu sain [9]. À ce jour, les médiateurs de cette fonction immunorégulatrice restent à préciser. Les lymphocytes T CD8+/CD57+ dans leur ensemble seraient impliqués dans l’inhibition des fonctions lymphocytaires T effectrices anti-infectieuses ou anti-tumorales ou encore dans l’homéostasie des lymphocytes T CD8+ dans leur ensemble afin d’en limiter l’expansion [10], [11], [12] and [13]. Ils semblent

être directement impliqués dans la réponse immunitaire adaptative anti-VIH alors qu’ils inhibent la réponse immunitaire en cas d’infection par le cytomégalovirus (CMV). Cette population peut également inhiber la génération de lymphocytes T cytotoxiques dirigés contre des lignées cellulaires autologues transformées par le virus Epstein Barr (EBV). Cet effet inhibiteur ne semble pas lié à des facteurs solubles ni à un effet cytotoxique direct exercé contre les lymphocytes transformés par l’EBV [10]. Ces lymphocytes disposent d’un répertoire du récepteur à l’antigène des lymphocytes T (TCR) limité avec une expression préférentielle de certaines chaînes Vβ comme les chaînes Vβ5 et Vβ13.

Breast milk also contains substantial amounts of intracellular ad

Breast milk also contains substantial amounts of intracellular adhesion molecule 1 and vascular adhesion molecule 1; low quantities of soluble S-selectin, l-selectin and CD14, which may mediate differentiation and growth of B cells [46]. Natural autoantibodies, thought to be important in the selection of the pre-immune B cell repertoire and in the development of immune tolerance,

are also detected in colostrum and in breast milk [48]. Recently, the beneficial effects of human oligosaccharides in prevention of neonatal diarrhoeal and respiratory tract infections have been highlighted [49] and [50]. Human breast milk is known to contain factors that can modulate toll-like receptor (TLR) Selleckchem PARP inhibitor signaling, including soluble TLR2, which can competitively inhibit signaling through membrane TLR2 [51], as well as a protein that inhibits TLR2-mediated and activates TLR4-mediated transcriptional responses

in human intestinal epithelial and mononuclear cells by an as-yet-unknown mechanism [52]. It has been speculated that reduced TLR2 responsiveness at birth may facilitate the normal establishment of beneficial Gram-positive bifidobacteria intestinal flora. Lipids present in human milk have been shown to inactivate GBS in vitro, providing additional benefit to protect from invasive infection at the mucosal surfaces [53]. Neonates have Rapamycin research buy low levels of SIgA and SIgM [54] thus protection from invasive pathogens enough at the mucosal surface relies on antibodies in breast milk. As antibody in breast milk is produced following antigenic stimulation of the maternal MALT and bronchial tree (bronchomammary pathway) [55], these antibodies are targeted to many infectious agents encountered by the mother both prior to birth and during the breastfeeding

period. It is currently hypothesized that SIgA represents the crucial primary protective component of breast milk [56] and [57]. SIgA protects against mucosal pathogens by immobilizing these, preventing their adherence to epithelial surfaces, or by neutralizing toxins or virulence factors. SIgA concentration is far higher in colostrum (12 mg/ml) than in that found in mature milk (1 mg/ml). A breastfed infant may ingest around 0.5–1.0 g of SIgA per day [40]. SIgA production is enhanced by Interleukin-6 (IL-6) whilst the production of secretory components is enhanced by TNF-α and TGF-β causes class switching towards B cells producing IgA [47], all of which are present in breast milk. SIgA antibodies present in breast milk are specific for numerous enteric and respiratory pathogens.

Chaque question est

cotée de 0 (aucune difficulté) à 5 (i

Chaque question est

cotée de 0 (aucune difficulté) à 5 (impossible à faire), avec un score total allant de 0 à 90. Il faut environ trois minutes pour le remplir. Nous avons Temozolomide évalué l’incapacité fonctionnelle de la main chez 50 patients souffrant de sclérodermie. Leur âge moyen était de 54 ± 12 ans et la durée d’évolution de la ScS de 11 ± 9 ans. Le score moyen de l’incapacité fonctionnelle de la main de Cochin était de 17 ± 16. Ce score était bien corrélé à la mobilité globale de la main et du poignet (mesurée par les indices de Keitel et Kapandji), à l’incapacité fonctionnelle globale (mesurée par le Health Assessment Questionnaire [HAQ]) et au handicap global (mesuré par l’échelle MACTAR). En revanche, il n’était pas corrélé à l’âge, à l’anxiété ou la dépression (mesurés par l’échelle HAD) ou à la durée d’évolution de la maladie. Enfin, l’incapacité fonctionnelle de la main de Cochin expliquait 75 % de l’incapacité fonctionnelle globale mesurée par le score HAQ. Ce questionnaire est en mesure d’évaluer les différences entre les patients ayant une forme diffuse ou limitée de Ruxolitinib cost ScS. Il peut également différencier ou non une atteinte articulaire des mains (arthralgies, arthrites, contractures en flexion) [29]. Nous avons

également mis en évidence l’impact des UD sur le handicap et la qualité de vie chez les patients atteints de ScS. Dans une étude menée chez 213 patients, un tiers d’entre eux avaient au moins un UD au moment de l’évaluation. Ces patients avaient des scores HAQ et un CHFS plus élevés, une limitation de la mobilité de la main et du poignet et

une altération de la composante psychique du SF36 [10]. Bien que non spécifiquement créé pour la ScS, le CHFS est utile pour prendre en charge les patients atteints de ScS. Il est facile à comprendre pour le patient, évalué rapidement et permet l’individualisation Cell press des patients avec atteinte articulaire et/ou une déficience microvasculaires de la main. En outre, il a montré une bonne sensibilité au changement chez les patients atteints de ScSet traités par un programme de rééducation de la main [29]. Le Hand Mobility Function ScaleS (HAMI), évaluant la mobilité de la main dans la sclérodermie, est un test basé sur la performance. Spécialement créé pour la ScS, c’est un outil fiable et valide [25]. Il est composé de neuf items et teste à la fois la flexion et l’extension des doigts, l’abduction du pouce, l’extension dorsale et la flexion du poignet, la pronation et la supination de l’avant-bras, la pince pouce-index et l’adduction des doigts. Les différentes zones du HAMIS explorées sont composées de poignées de différentes tailles et de différents mouvements, tous liés à des outils et des gestes qui font partie des activités quotidiennes.

Lorsqu’elle

devient pathogène, cette expansion se manifes

Lorsqu’elle

devient pathogène, cette expansion se manifeste alors par un tableau d’infiltration des tissus comme au cours du syndrome d’infiltration diffuse à lymphocytes T CD8+ chez les patient infecté par le VIH, dans un contexte de déficit immunitaire ou de maladie du greffon contre l’hôte. Ailleurs, elle peut s’associer à des cytopénies comme en particulier selleck chemical des neutropénies immunologiques. Une expansion de lymphocytes T CD8+/CD57+ peut être mise en évidence à partir de l’étude des lymphocytes circulants, dont le phénotype peut montrer une augmentation de la population de lymphocytes T CD8+/CD57+ qui représente alors plus de 30 % des lymphocytes totaux. Panobinostat mouse L’existence d’une hyperlymphocytose le plus souvent modérée est particulièrement évocatrice d’une expansion lymphocytaire T CD8+/CD57+. Cependant, un taux normal de lymphocytes totaux n’exclut pas le diagnostic et un phénotypage lymphocytaire doit être demandé si le tableau clinique est évocateur même si le taux de lymphocytes totaux est dans les limites de la normale. Le diagnostic d’expansion de lymphocytes T CD8+/CD57+

peut également être anatomopathologique, à partir d’une biopsie d’organe infiltré [27]. Enfin, ces expansions doivent être distinguées des lymphoproliférations clonales à LGL (ou leucémies à LGL) qui sont des maladies malignes [2]. Dans toute situation où une expansion lymphocytaire T CD8+/CD57+ est importante, son interprétation doit inclure une analyse cytologique, une étude de la clonalité et éventuellement une analyse cytogénétique afin de ne pas méconnaître une leucémie à LGL. Au cours de l’infection par le VIH, la population

lymphocytaire T CD8+ s’expand précocement et le plus souvent transitoirement et s’intègre dans le cadre de la réponse immunitaire contre le virus. Un renouvellement accéléré des clones de lymphocytes T CD8+ anti-VIH permettrait Bay 11-7085 de remplacer les clonotypes CD57+ faisant l’objet d’un processus de sénescence réplicative. Leur activité immunomodulatrice pourrait contribuer à la survenue d’infections opportunistes et de néoplasies chez les sujets séropositifs pour le VIH avec un taux normal de lymphocytes T CD4+ et une charge virale indétectable [28]. Dans ce contexte, une expansion de lymphocytes T CD8+/CD57+ peut être à l’origine d’une hyperlymphocytose T CD8+ isolée (parfois découverte lors d’un phénotypage systématique) [29] ou s’intégrer dans le cadre d’un syndrome d’infiltration diffuse à lymphocytes T CD8+ (DILS). La frontière entre ces deux entités est difficile à cerner.

The smaller the effect of vaccine on progression to disease, the

The smaller the effect of vaccine on progression to disease, the more closely VE-acq can predict VE-disease (see Fig. 1). The consideration of NP carriage as part of the licensure pathway emerged from the need for a MDV3100 solubility dmso more direct measurement of vaccine efficacy to evaluate non-conjugate vaccines, new dosing schedules, expanded serotype coverage

and impact in varied geographic and epidemiological settings. Described by Professor David Goldblatt and Dr. Debby Bogaerts, there are advantages and disadvantages to the inclusion of NP carriage as a surrogate for disease protection in vaccine trials. NP carriage can serve as a functional biological assay that is relatively

easy to measure and that has a high negative predictive value of an individual’s risk for pneumococcal disease. VE-col also provides information about the population-level impact of vaccination because if there is no carriage, there is no risk of transmission of pneumococcus, and thus carriage prevention predicts the indirect effect of vaccine Selleck Androgen Receptor Antagonist introduction. Since NP carriage of pneumococcus is a more common outcome than disease endpoints, vaccine trials looking at carriage can be powered with smaller sample sizes. Some drawbacks to considering NP carriage data in vaccine trials include low positive predictive value of NP carriage as a surrogate marker for disease: not all serotypes causing IPD are detected regularly in NP sampling (e.g. serotypes 1 and 5) and not all carried serotypes are significant causes

of disease. Pneumococcal NP carriage itself is a dynamic event that is influenced by competing NP flora, immune fitness of the host, and density of colonization. These factors may present real differences in an individual’s risk for disease in a clinical trial setting. Adenylyl cyclase Finally, there are potential confounders in a clinical study of NP carriage that need to be considered a priori such as antibiotic use and the impact of breastfeeding. The implications for the pneumococcal licensure pathway – in fact for the licensure pathway for any vaccine based on a carrier state – involve advantages and disadvantages. Taking the potential pros and cons into account (summarized in Table 2), the use of NP carriage data as supporting evidence in the vaccine licensure pathway for those products with an articulated licensure mechanism is most likely to be least contentious as a way forward. At the start of the second day of the consultation, two specific questions were posed to vaccine manufacturers and regulators: (1) are there different approaches based on the pneumococcal vaccine product type to be licensed, e.g.