Persistent Carriers Research Articles

Selected Factors of Innate Immunity in Healthy Individuals with S. aureus Nasal Carriage.

Nasal carriage of Staphylococcus aureus represents a well-defined factor of risk involving community and hospital-acquired infections. Recently a significance of several host factors has been pointed out and, in particular, of immune determinants in nasal S. aureus colonization. Therefore, this study aimed at analysis of manifestation involving manifestation in the nasal secretions of important components of the host innate immunity – human beta-defensin-2 (HBD-2), lysozyme (Ly), and interferon-gamma (IFN-γ) in healthy individuals and in persons with persistent carriage of S. aureus. The studies were conducted in two groups of healthy volunteers, encompassing non-carriers (group 1) or persistent carriers of S. aureus (group 2). Elisa assays were employed to evaluate levels of HBD-2, Ly, and IFN-γ in nasal secretions of the examined donors. In S. aureus carriers a significant variability of HBD-2 levels was detected, corresponding to, respectively, the high (averaging at 1.46 ng/ml) and the low (averaging at 0.13 ng/ml) secretory response of the defensin. The level of Ly in S. aureus carriers averaged at 1.46 μg/ml and it manifested no significant difference as compared to that noted in non-carriers. In turn, concentrations of IFN-γ in nasal secretions in the group of carriers of S. aureus amounted on the average to 81.7 pg/ml and they were 1.3-fold higher that in the group of non-carriers. The obtained results allow to conclude that IFN-γ secretion by the nasal cavity-colonizing S. aureus remains quantitatively insufficient to eliminate the pathogen. Nevertheless, a significant increase in levels of this host factor may be important for restriction of the staphylococcal colonization and protection against development of an invasive infection. In turn, the role of HBD-2 and Ly in inactivation of the colonizing S. aureus remains doubtful.

Health and health-related quality of life in pig farmers carrying livestock-associated methicillin-resistant Staphylococcus aureus.

There is limited knowledge about the effect of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) carriage on health-related quality of life (QoL). With this study, we explored whether LA-MRSA causes infections or affects health-related QoL in pig farmers. This prospective cohort study surveyed persons working on 49 farrowing pig farms in The Netherlands for 1 year (2010-2011). On six sampling moments, nasal swabs, environmental samples and questionnaires on activities and infections were collected. At the end of the study year, persons were asked about their QoL using the validated SF-36 and EQ-5D questionnaires. Of 120 persons, 44 (37%) were persistent MRSA carriers. MRSA carriage was not associated with infections, use of antimicrobials, healthcare contact and health-related QoL items in univariate or multivariate analysis, most likely due to the 'healthy worker effect'. Despite high carriage rates, the impact of LA-MRSA carriage in this population of relatively healthy pig farmers on health and health-related QoL appears limited; more research is needed for confirmation.

The turnover of strains in intermittent and persistent nasal carriers of Staphylococcus aureus

We aimed to examine the dynamics of Staphylococcus aureus nasal carriage in healthy adults. Selected S. aureus strains isolated from weekly nasal swabs obtained from 122 healthy young adults over a 13 week period were spa typed. The median duration of intermittent carriage was 4 weeks (IQR 2-6) and the median interval between episodes of carriage of different spa types was 3.5 weeks (IQR 2.25-4). 6/19 (32%) Persistent carriers were colonised with more than one spa type during the study, and in two persistent carriers a brief period of mixed colonisation with two spa types was observed. Even when the carriage strain changed, it was very rare for persistent carriers to have a period during which they were culture-negative (only 6/188 (3%) swabs submitted by persistent carriers failed to culture S. aureus). Our results imply that at least every eight weeks a healthy young adult is exposed to S. aureus sufficient to cause a new episode of carriage among intermittent carriers. Persistent carriers are almost always colonised with S. aureus and over the course of a year there will be at least one replacement of the dominant strain.

Genetic variants in IL12 influence both hepatitis B virus clearance and HBV-related hepatocellular carcinoma development in a Chinese male population.

IL12 plays a major role not only in inducing appropriate immune responses against viral infections (including HBV) but also in the antitumor immune response. This study was conducted to investigate the relationships of genetic variants in IL12 with hepatitis B virus (HBV) clearance and development of HBV-related hepatocellular carcinoma (HCC). We genotyped three single nucleotide polymorphisms (SNPs) of the IL12A (rs568406 and rs2243115) and IL12B (rs3212227) in 395 HBV-positive HCC patients, 293 persistent HBV carriers and 686 subjects with HBV natural clearance from southern China, using the improved multiplex ligase detection reaction (iMLDR) method. Logistic regression analysis adjusted for age, smoking, and alcohol consumption status showed that rs568408 variant genotypes were significantly associated with host HBV-related HCC risk when compared with persistent HBV carriers, and carriers of the GA + AA genotype decreased the HCC risk in comparison with GG carriers (adjusted OR = 0.53, 95% CI 0.35-0.80, P = 0.002). No relationships between the rs2243115 and rs3212227 SNPs and HCC risk were observed (all P > 0.05). Besides, rs568408 showed an approaching significant effect on susceptibility to HBV persistent infection (adjusted OR = 1.34, 95% CI 0.99-1.81, P = 0.057 in dominant genetic models). Furthermore, the TG haplotype was observed to be associated with a significantly increased risk of HBV-related HCC (OR = 1.42, 95% CI 1.10-1.83, P = 0.006), while TA haplotype was associated with a decreased risk of HBV-related HCC (OR = 0.61, 95% CI 0.45-0.83, P = 0.002). Our results reveal that the IL12A rs568408 variant may be a marker SNP for risk of both HBV clearance and HBV-related HCC development.

Genome-wide association study reveals a locus for nasal carriage of Staphylococcus aureus in Danish crossbred pigs.

BackgroundStaphylococcus aureus is an important human opportunistic pathogen residing on skin and mucosae of healthy people. Pigs have been identified as a source of human colonization and infection with methicillin-resistant Staphylococcus aureus (MRSA) and novel measures are needed to control zoonotic transmission. A recent longitudinal study indicated that a minority of pigs characterized by high nasal load and stable carriage may be responsible for the maintenance of S. aureus within farms. The primary objective of the present study was to detect genetic loci associated with nasal carriage of S. aureus in Danish crossbred pigs (Danish Landrace/Yorkshire/Duroc).ResultsFifty-six persistent carriers and 65 non-carriers selected from 15 farms surveyed in the previous longitudinal study were genotyped using Illumina’s Porcine SNP60 beadchip. In addition, spa typing was performed on 126 S. aureus isolates from 37 pigs to investigate possible relationships between host and S. aureus genotypes. A single SNP (MARC0099960) on chromosome 12 was found to be associated with nasal carriage of S. aureus at a genome-wide level after permutation testing (p = 0.0497) whereas the association of a neighboring SNP was found to be borderline (p = 0.114). Typing of S. aureus isolates led to detection of 11 spa types belonging to the three main S. aureus clonal complexes (CC) previously described in pigs (CC9, CC30 and CC398). Individual carriers often harbored multiple S. aureus genotypes and the host-pathogen interaction seems to be independent of S. aureus genotype.ConclusionOur results suggest it may be possible to select pigs genetically resistant to S. aureus nasal colonization as a tool to control transmission of livestock-associated MRSA to humans.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-015-0599-y) contains supplementary material, which is available to authorized users.

Impact of Host Heterogeneity on the Efficacy of Interventions to Reduce Staphylococcus aureus Carriage.

Staphylococcus aureus is a common cause of bacterial infections worldwide. It is most commonly carried in and transmitted from the anterior nares. Hosts are known to vary in their proclivity for S. aureus nasal carriage and may be divided into persistent carriers, intermittent carriers, and noncarriers, depending on duration of carriage. Mathematical models of S. aureus to predict outcomes of interventions have, however, typically assumed that all individuals are equally susceptible to colonization. To characterize biases created by assuming a homogeneous host population in estimating efficacy of control interventions. Mathematical model. We developed a model of S. aureus carriage in the healthcare setting under the homogeneous assumption as well as a heterogeneous model to account for the 3 types of S. aureus carriers. In both models, we calculated the equilibrium carriage prevalence to predict the impact of control measures (reducing contact and decolonization). The homogeneous model almost always underestimates S. aureus transmissibility and overestimates the impact of intervention strategies in lowering carriage prevalence compared to the heterogeneous model. This finding is generally consistent regardless of changes in model setting that vary the proportions of various carriers in the population and the duration of carriage for these carrier types. Not accounting for host heterogeneity leads to systematic and substantial biases in predictions of the effects of intervention strategies. Further understanding of the clinical impacts of heterogeneity through modeling can help to target control measures and allocate resources more efficiently.

Hepatitis B virus genotype, mutations, human leukocyte antigen polymorphisms and their interactions in hepatocellular carcinoma: a multi-centre case-control study.

Three genome-wide association studies (GWAS) have been conducted on the genetic susceptibility of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), two of which consistently identified tagging single nucleotide polymorphisms (SNPs) around HLA-DQ/DR. In contrast, large multi-centre association studies between HBV genotype, mutations and the risk of HCC are relatively rare, and their interactions with host variants are even less. We performed a multi-centre study of 1,507 HBV-related HCC cases and 1,560 HBV persistent carriers as controls to evaluate the effects of HBV genotype, mutations, GWAS-identified HLA-DQ/DR SNPs (rs9272105 and rs9275319) and their interactions on HCC risk. We found HBV genotype C was more frequent in HBV-related HCC. And 11 HBV hotspot mutations were independently and significantly associated with HCC risk. We also detected significant interactions of rs9272105 with both the HBV genotype and mutations. Through stepwise regression analysis, HBV genotype, the 11 mutations, HLA-DQ/DR SNPs, and the interaction of rs9272105 with mutation A1752G were all entered into the HCC prediction model, and the area under the curve for the panel including the HLA-DQ/DR SNPs, HBV genotype and mutations was 0.840. The HBV genotype, the mutations and the HLA-DQ/DR SNPs may serve as biomarkers for the surveillance of HBV persistent carriers.

Phenotypic heterogeneity and temporal expression of the capsular polysaccharide in Staphylococcus aureus.

Bacteria respond to ever-changing environments through several adaptive strategies. This includes mechanisms leading to a high degree of phenotypic variability within a genetically homogeneous population. In Staphylococcus aureus, the capsular polysaccharide (CP) protects against phagocytosis, but also impedes adherence to endothelial cells and/or matrix proteins. We analysed the regulation of core biosynthesis genes (capA-P) necessary for CP synthesis using single-cell assays (immunofluorescence and promoter-activity). In persistent human carriers, we found a distinct subpopulation of nasal S. aureus to be CP positive. In vitro, cap expression is also heterogeneous and strongly growth-phase dependent. We asked whether this peculiar expression pattern (earlyOff/lateHeterogen) is orchestrated by the quorum system Agr. We show that the Agr-driven effector molecule RNAIII promotes cap expression largely via inactivation of the repressor Rot. High NaCl, deletion of CodY or Sae also resulted in higher cap expression but did not change the earlyOFF/lateHeterogen expression pattern. Activity of the quorum system itself is largely homogenous and does not account for the observed heterogeneity of cap expression or the strictly growth phase dependent expression. Our findings are in contrast to the prevailing view that quorum sensing is the main driving force for virulence gene expression when bacterial cell densities increase.

Prevalence of enterotoxin genes in Staphylococcus aureus colonising food handlers: does nasal carriage status matter?

This study investigated the association between the presence of staphylococcal enterotoxin (SE) genes and nasal carriage status, and determined temporal changes in the prevalence of these genes in Staphylococcus aureus strains isolated from healthy carriers between 2002 and 2011. Three large samples of food handlers recruited in 2002, 2003 and 2011 were nasally sampled on two occasions to determine S. aureus colonisation status. Those carrying the same spa type on both occasions were defined as persistent carriers. Genes for SEs SEA-SEU were amplified and associations between carriage status and presence of SE genes were investigated. Although 80% of nasal isolates harboured at least one SE gene over the sampling period, persistent carriers were significantly more likely to harbour enterotoxigenic S. aureus than transiently colonised subjects [odds ratio (OR) 2.52-3.06]. Strains from persistent carriers more commonly harboured sea, seb and sem. The prevalence of classical SE genes and sej, sem, sen, seo, seq and ses was stable over time, but seh, sel, sep, ser, set and selu increased significantly. Increased toxigenicity of isolates from persistent carriers is consistent with the elevated antibody levels to classical SEs previously reported in persistent carriers, supporting the hypothesis that superantigen production in the nasal cavity may enhance colonisation.

Abstract 850: Hepatitis B virus genotype, mutations, human leukocyte antigen polymorphisms and their interactions in hepatocellular carcinoma: a multi-centre case-control study

Abstract Objective:Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Our aim was to evaluate the effects of the hepatitis B virus (HBV) genotype, mutations, HLA single nucleotide polymorphisms (SNPs) and their interactions on HCC risk. Methods: A multi-centre case-control study of 1,507 HBV-related HCC cases and 1,560 HBV persistent carriers as controls was performed. HBV genotype, mutations and genome-wide association studies (GWAS)-identified HLA-DQ/DR SNPs (rs9272105 and rs9275319) were detected. Results: We found that the frequencies of the HBV genotypes B and BC (coinfection) were varied among the studied areas, but genotype C was consistently more frequent in HBV-related HCC (80.6% among HCC vs. 34.4% among the controls). Moreover, 11 HBV hotspot mutations in the EnhII/BCP/PC region were independently and significantly associated with HCC risk. We also detected significant interactions of HLA-DQ/DR rs9272105 with both the HBV genotype and mutations (P < 0.05 for each), but there were not significant interactions for rs9275319. Through a stepwise regression analysis, the HBV genotype, the 11 mutations, HLA-DQ/DR rs9272105 and rs9275319, and the interaction of the mutation A1752G with rs9272105 were all entered into the prediction model of HCC, and the area under the curve (AUC) for the panel including the HLA-DQ/DR SNPs, HBV genotype and mutations was 0.840 (sensitivity = 81.3%, specificity = 74.8%). Conclusions: The HBV genotype, the mutations and the HLA-DQ/DR SNPs may serve as biomarkers for the surveillance of HBV persistent carriers. Large studies with prospective designs are warranted to further evaluate our results. Note: This abstract was not presented at the meeting. Citation Format: Juan Wen, Ci Song, Deke Jiang, Tianbo Jin, Xiangjun Zhai, Jianfeng Xu, Hongbing Shen, Zhibin Hu. Hepatitis B virus genotype, mutations, human leukocyte antigen polymorphisms and their interactions in hepatocellular carcinoma: a multi-centre case-control study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 850. doi:10.1158/1538-7445.AM2015-850

The Dynamic of Staphylococcus aureus Nasal Carriage in Central Iran.

Background:Nasal carriage of Staphylococcus aureus plays an important role in the pathogenesis of staphylococcal infections. Anterior nasal region is a primary origin of S. aureus. In longitudinal studies, three types of S. aureus nasal carriers can be distinguished: persistent carriers, intermittent or transient carriers, and noncarriers.Objectives:This study was designed to determine the dynamic of S. aureus nasal carriage in healthy carriers of central Iran.Patients and Methods:A total of 813 healthy adults were subjected to this cross-sectional study from November 2011 to January 2012 in Arak University of Medical Sciences. Two anterior nasal swabs were taken with a week interval from each participant. All the isolates were identified as S. aureus phenotypically by standard laboratory methods. The isolates were reconfirmed by amplification of sa442 gene as the identification marker. All the isolates were screened for the presence of the PVL (Panton-Valentine leukocidin) virulence genes and arginine catabolic mobile element (ACME-arc).Results:Among the 813 subjects screened, 83 (10.2%) were persistent carriers, 86 (10.6%) were transient carriers and 644 (79.2%) cases were found as noncarriers. A total of 169 (20.8%) participants had colonized S. aureus. The frequency of ACME–arc A and PVL genes in S. aureus strains were 17% and 20%, respectively.Conclusions:Carriage of PVL-positive S. aureus is common in this region, even in the low frequency of MRSA colonization. The detection of ACME-arcA gene in S. aureus isolates is a public-health concern and demands continued surveillance and close monitoring.

Livestock-associated MRSA in household members of pig farmers: transmission and dynamics of carriage, a prospective cohort study.

This prospective cohort study describes carriage of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in household members from 49 farrowing pig farms in the Netherlands (2010–2011). Of 171 household members, 4% were persistent MRSA nasal carriers, and the MRSA prevalence on any given sampling moment was 10% (range 7-11%). Working in the stables (of which 98% was MRSA-positive, prevalence ratio (PR) = 2.11 per 10 hours), working with sows (PR=1.97), and living with an MRSA-positive pig farmer (PR=4.63) were significant determinants for MRSA carriage. Significant protective factors were carriage of methicillin-susceptible Staphylococcus aureus (MSSA) (PR=0.50), and wearing a facemask when working in the stables (37% decreased prevalence). All MRSA strains during the study period were known livestock-associated types. The bacteriophage φ3 was not found in household members. Transmission from pigs and the environment appeared to be important determinants; human-to-human transmission could not sufficiently be differentiated. Wearing a facemask when working in the stables and carriage of MSSA are potential interventional targets.

Association of polymorphisms in HLA antigen presentation-related genes with the outcomes of HCV infection.

Antigen-presentation genes play a vital role in the pathogenesis of HCV infection. However, the relationship of variants of these genes with spontaneous outcomes of HCV infection has not been fully investigated. To explore novel loci in the Chinese population, 34 tagging-SNPs in 9 candidate genes were genotyped for their associations with the outcomes of HCV infection. The distributions of different genotypes and haplotypes were compared among 773 HCV-negative controls, 246 subjects with HCV natural clearance, and 218 HCV persistent carriers recruited from hemodialysis patients and intravenous drug users. Our study implicated that TAP2, HLA-DOA, HLA-DOB, and tapasin loci were novel candidate regions for susceptibility to HCV infection and viral clearance in the Chinese population. Logistic regression analyses showed that TAP2 rs1800454 A (OR = 1.48, P = 0.002) and HLA-DOB rs2071469 G (OR = 1.23, P = 0.048) were significantly associated with increased susceptibility to establishment of HCV infection. However, high-risk behavior exposure and age were stronger predictors of HCV infection. Mutation of tapasin rs9277972 T (OR = 1.57, P =0.043) increased the risk of HCV chronicity, and HLA-DOA rs3128935 C (OR = 0.62, P = 0.019) increased the chance of viral resolution. With regards to the effect of rs3128925, interactions were found with high-risk behavior (P = 0.013) and age (P = 0.035). The risk effect of rs3128925 T for persistent HCV infection was higher in injecting drug users (vs. dialysis patients) and in subjects ≥ 40 years old (vs. < 40 years old).

Does the superantigen profile of Staphylococcus aureus strains isolated from persistent nasal carriers change?

Does the superantigen profile of Staphylococcus aureus strains isolated from persistent nasal carriers change?

Nasal carriage of Staphylococcus aureus among the interns before and after posting in the department of surgery at a tertiary care hospital

Context: Staphylococcus aureus could be a commensal in the anterior nares of a health-care personnel. There are no studies on Staphylococcal nasal carriage among interns before and after posting in the department of surgery. Aims: To find out the prevalence of Methicillin-sensitive S. aureus (MSSA) and Methicillin-resistant S. aureus (MRSA) among interns before and after the surgical posting. Settings and Design: A cross-sectional study was carried out on interns at the time of entry and exit from their surgical posting in a tertiary care hospital. Methods and Material: Paired nasal swabs, collected at the entry and exit, from anterior nares of 130 interns during their 60-day surgical posting, were cultured, and Methicillin-sensitive S. aureus (MSSA) and MRSA were detected. The sensitivity pattern of MRSA strains was determined. The knowledge of spread and prevention of MRSA among interns was assessed. Results: MSSA was detected in the anterior nares of 36 (27.7%) interns at entry had dropped significantly to 19 (14.6%) by the end of the surgical posting. The prevalence of MRSA rose from 6 (4.6%) to 8 (6.2%) by the end. Autoinfections among two persistent carriers were detected. Out of 88 interns who had normal flora, 84 (95.5%) retained it after the surgery posting. Among the 14 MRSA strains isolated in the study, 12 (85.7%) were resistant to Ciprofloxacin, 7 (50%) were resistant to Erythromycin, and 4 (28.6%) were resistant to Clindamycin. Almost half of the interns, who responded to a questionnaire, were unaware of the mode of spread of MRSA and measures to prevent it. Conclusions: Nineteen (14.6%) interns in our study were intermittent carriers of S. aureus. Interns need to be educated on the spread and prevention of Staphylococcal infections.

Individual predisposition to Staphylococcus aureus colonization in pigs on the basis of quantification, carriage dynamics, and serological profiles.

Previous research on Staphylococcus aureus in pigs focused on livestock-associated methicillin-resistant S. aureus (MRSA) and had a qualitative cross-sectional design. This study aimed to elucidate the frequency, load, and stability of S. aureus nasal carriage in pigs over time and investigated possible associations between carriage and immune response. Nasal swabs were collected three times weekly from 480 tagged adult pigs in 20 Danish production farms. S. aureus and MRSA were quantified on selective media by the most-probable-number method. The levels of IgG against 10 S. aureus antigens in serum were quantified in selected pigs by a Luminex assay. All the farms were positive for S. aureus and 15 for MRSA, leading to overall prevalences of persistent and intermittent carriers and noncarriers of 24, 52, and 23%, respectively. Carriage frequency and nasal loads were significantly higher on MRSA-positive farms. Logistic-regression modeling revealed the presence of individual pigs characterized by high nasal loads (>10,000 CFU per swab) and stable carriage regardless of farm- and pen-associated factors. On the other hand, the humoral response was strongly influenced by these environmental factors. The existence of a minority of shedders contributing to maintenance of S. aureus within farms opens up new perspectives on the control of MRSA in pig farming.

Methicillin-resistant Staphylococcus aureus: site of acquisition and strain variation in high-risk nursing home residents with indwelling devices.

Characterize the clinical and molecular epidemiology of new methicillin-resistant Staphylococcus aureus (MRSA) acquisitions at nasal and extranasal sites among high-risk nursing home (NH) residents. Multicenter prospective observational study. Six NHs in southeast Michigan. A total of 120 NH residents with an indwelling device (feeding tube and/or urinary catheter). Active surveillance cultures from the nares, oropharynx, groin, perianal area, wounds (if present), and device insertion site(s) were collected upon enrollment, at day 14, and monthly thereafter. Pulsed-field gel electrophoresis and polymerase chain reaction for SCCmec, agr, and Panton-Valentine leukocidin were performed. Of 120 participants observed for 16,290 device-days, 50 acquired MRSA (78% transiently, 22% persistently). New MRSA acquisitions were common in extranasal sites, particularly at device insertion, groin, and perianal areas (27%, 23%, and 17.6% of all acquisitions, respectively). Screening extranasal sites greatly increases the detection of MRSA colonization (100% of persistent carriers and 97.4% of transient carriers detected with nares, groin, perianal, and device site sampling vs 54.5% and 25.6%, respectively, for nares samples alone). Colonization at suprapubic urinary catheter sites generally persisted. Healthcare-associated MRSA (USA100 and USA100 variants) were the dominant strains (79.3% of all new acquisition isolates). Strain diversity was more common in transient carriers, including acquisition of USA500 and USA300 strains. Indwelling device insertion sites as well as the groin and perianal area are important sites of new MRSA acquisitions in NH residents and play a role in the persistency of MRSA carriage. Clonal types differ among persistent and transient colonizers.

IgG4 subclass-specific responses to Staphylococcus aureus antigens shed new light on host-pathogen interaction.

IgG4 responses are considered indicative for long-term or repeated exposure to particular antigens. Therefore, studying IgG4-specific antibody responses against Staphylococcus aureus might generate new insights into the respective host-pathogen interactions and the microbial virulence factors involved. Using a bead-based flow cytometry assay, we determined total IgG (IgGt), IgG1, and IgG4 antibody responses to 40 different S. aureus virulence factors in sera from healthy persistent nasal carriers, healthy persistent noncarriers, and patients with various staphylococcal infections from three distinct countries. IgGt responses were detected against all tested antigens. These were mostly IgG1 responses. In contrast, IgG4 antibodies were detected to alpha-toxin, chemotaxis inhibitory protein of S. aureus (CHIPS), exfoliative toxins A and B (ETA and -B), HlgB, IsdA, LukD, -E, -F, and -S, staphylococcal complement inhibitor (SCIN), staphylococcal enterotoxin C (SEC), staphylococcal superantigen-like proteins 1, 3, 5, and 9 (SSL1, -3, -5, and -9), and toxic shock syndrome toxin 1 (TSST-1) only. Large interpatient variability was observed, and the type of infection or geographical location did not reveal conserved patterns of response. As persistent S. aureus carriers trended toward IgG4 responses to a larger number of antigens than persistent noncarriers, we also investigated sera from patients with epidermolysis bullosa (EB), a genetic blistering disease associated with high S. aureus carriage rates. EB patients responded immunologically to significantly more antigens than noncarriers and trended toward even more responses than carriers. Altogether, we conclude that the IgG4 responses against a restricted panel of staphylococcal antigens consisting primarily of immune modulators and particular toxins indicate important roles for these virulence factors in staphylococcal pathogen-host interactions, such as chronicity of colonization and/or (subclinical) infections.

Dynamics of methicillin-resistant Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus carriage in pig farmers: a prospective cohort study

Our purpose was to determine the dynamics of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) carriage and its determinants in persons working at pig farms, in order to identify targets for interventions. This prospective cohort study surveyed 49 pig farms in the Netherlands on six sampling dates in 1 year (2010-11). Nasal and oropharyngeal swabs were collected, as well as environmental surface samples from stables and house. Of 110 pig farmers, 38% were persistent MRSA nasal carriers. The average cross-sectional MRSA prevalence was 63%. Methicillin-susceptible S. aureus (MSSA) nasal carriage was associated with fewer MRSA acquisitions (prevalence rate (PR) = 0.47, p 0.02). In multivariate analysis, an age of 40-49 years (PR = 2.13, p 0.01), a working week of ≥40 h (PR=1.89, p 0.01), giving birth assistance to sows (PR=2.26, p 0.03), removing manure of finisher pigs (PR=0.48, p 0.02), and wearing a facemask (PR = 0.13, p 0.02) were significantly related with persistent MRSA nasal carriage. A higher MRSA exposure in stables was associated with MRSA in pig farmers (p <0.0001). This study describes a very high prevalence of LA-MRSA carriage in pig farmers, reflecting extensive exposure during work. We identified the possible protective effects of MSSA carriage and of continuously wearing a facemask during work.

Staphylococcus aureus nasal carriage might be associated with vitamin D receptor polymorphisms in type 2 diabetes

Vitamin D receptor (VDR) gene polymorphisms have been associated with susceptibility to several diseases, including type 1 diabetes (T1D), type 2 diabetes (T2D), and various infections. The study investigated whether VDR gene polymorphisms influence nasal carriage of Staphylococcus aureus in individuals with T2D, an important source for bloodstream, surgical site and other nosocomial infections. In 173 patients with T2D genotyped for the VDR gene polymorphisms on FokI (rs10735810) F>f, BsmI (rs1544410) B>b, ApaI (rs7975232) A>a, and TaqI (rs731236) T>t, a nasal swab was obtained to detect colonization by S. aureus. A repeat swab was obtained in 162/173 subjects for the estimation of persistent S. aureus carriage. The prevalence of S. aureus nasal colonization was 19.7% and of persistent carriage was 8.6%. Nasal colonization by S. aureus was more common in individuals with FokI f allele than F allele (p 0.05; OR 1.69, 95% CI 1.00–2.89) and individuals with FokI ff genotypes were more frequently colonized than those with FokI FF and Ff genotypes combined (p 0.03; OR 2.61, 95% CI 1.14–5.99). The presence of the FokI f allele was related to higher rates of S. aureus persistent nasal colonization (p 0.002; OR 3.53, 95% CI 1.56–7.98), and individuals with a FokI ff genotype were more often persistent carriers than those with FokI FF and Ff genotypes combined (p <0.001; OR 7.32, 95% CI 2.39–22.41). This study is the first, to our knowledge, to show an association between FokI polymorphism in the VDR gene and nasal carriage of S. aureus in individuals with T2D.