Extensive genetic and biological characterization of infectious bronchitis virus strain D2860 of genotype GVIII.

Infectious bronchitis virus (IBV) strains of genotype GVIII have been emerging in Europe in the last decade, but no biological characterization has been reported so far. This paper reports the extensive genetic and biological characterization of IBV strain D2860 of genotype GVIII which was isolated from a Dutch layer flock that showed a drop in egg production. Whole genome sequencing showed that it has a high similarity (95%) to CK/DE/IB80/2016 (commonly known as IB80). Cross-neutralization tests with antigens and serotype-specific antisera of a panel of different non-GVIII genotypes consistently gave less than 2% antigenic cross-relationship with D2860. Five experiments using specified pathogen-free chickens of 0, 4, 29 and 63 weeks of age showed that D2860 was not able to cause clinical signs, drop in egg production, false layers or renal pathology. There was also a distinct lack of ciliostasis at both 5 and 8 days post-inoculation at any age, despite proof of infection by immunohistochemical (IHC) staining, RT-PCR and serology. IHC showed immunostaining between 5 and 8 days post inoculation in epithelial cells of sinuses and conchae, while only a few birds displayed immunostaining in the trachea. In vitro comparison of replication of D2860 and M41 in chicken embryo kidney cells at 37°C and at 41°C indicated that D2860 might have a degree of temperature sensitivity that might cause it to prefer the colder parts of the respiratory tract.

Genetic analysis of infectious bronchitis virus (IBV) in vaccinated poultry populations over a period of 10 years.

Infectious bronchitis virus (IBV) is an avian pathogen from the Coronavirus family causing major health issues in poultry flocks worldwide. Because of its negative impact on health, performance, and bird welfare, commercial poultry are routinely vaccinated by administering live attenuated virus. However, field strains are capable of rapid adaptation and may evade vaccine-induced immunity. We set out to describe dynamics within and between lineages and assess potential escape from vaccine-induced immunity. We investigated a large nucleotide sequence database of over 1700 partial sequences of the S1 spike protein gene collected from clinical samples of Dutch chickens submitted to the laboratory of Royal GD between 2011 and 2020. Relative frequencies of the two major lineages GI-13 (793B) and GI-19 (QX) did not change in the investigated period, but we found a succession of distinct GI-19 sublineages. Analysis of dN/dS ratio over all sequences demonstrated episodic diversifying selection acting on multiple sites, some of which overlap predicted N-glycosylation motifs. We assessed several measures that would indicate divergence from vaccine strains, both in the overall database and in the two major lineages. However, the frequency of vaccine-homologous lineages did not decrease, no increase in genetic variation with time was detected, and the sequences did not grow more divergent from vaccine sequences in the examined time window. Concluding, our results show sublineage turnover within the GI-19 lineage and we demonstrate episodic diversifying selection acting on the partial sequence, but we cannot confirm nor rule out escape from vaccine-induced immunity.RESEARCH HIGHLIGHTSSuccession of GI-19 IBV variants in broiler populations.IBV lineages overrepresented in either broiler, or layer production chickens.Ongoing episodic selection at the IBV S1 spike protein gene sequence.Several positively selected codons coincident with N-glycosylation motifs.

Atopic Manifestations Are Underestimated Clinical Features in Various Primary Immunodeficiency Disease Phenotypes.

BACKGROUND AND OBJECTIVES: Atopic manifestations are described as a clinical feature of various primary immunodeficiency disease (PID) phenotypes and are frequently reported in combined immunodeficiencies. The prevalence of atopic manifestations in other PIDs remains largely unknown. Objective: To evaluate the prevalence of atopic manifestations in PIDs other than combined immunodeficiencies and to identify in which PIDs atopic manifestations are most common with the aim of improving patient care. METHODS: A partner-controlled, questionnaire-based study was performed in pediatric and adult PID patients. Data from diagnostic tests to assess atopic manifestations (ie, diagnostic criteria for atopic dermatitis, spirometry, specific IgE against food and inhalant allergens) were collected from adult patients to confirm patient-reported atopic manifestations. RESULTS: Forty-seven children and 206 adults with PIDs and 56 partner-controls completed the questionnaire. Thirty-five pediatric patients (74.5%) and 164 adult patients (79.6%) reported having experienced 1 or more atopic manifestations compared with 28 partner-controls (50.0%). In the comparison of adult patients with partner-controls, prevalence values were as follows: atopic dermatitis, 49.5% vs 27.3% (P=.003); food allergy, 10.7% vs 1.9% (P=.031); asthma, 55.7% vs 14.8% (P<.001); and allergic rhinitis, 49.8% vs 21.8% (P<.001). The frequency of current atopic manifestations reported by patients was higher than the prevalence based on diagnostic tests (atopic dermatitis, 11.2%; food allergy, 1.9%; asthma 16.4%; and allergic rhinitis, 11.5%). CONCLUSION: Atopic manifestations are prevalent clinical features across a broad spectrum of PIDs and, in our cohort, frequently present in patients with combined immunodeficiencies and predominant antibody deficiencies. Atopic manifestations should be evaluated in patients with PIDs.

Fluorescence grid analysis for the evaluation of piecemeal surgery in sinonasal inverted papilloma: a proof-of-concept study.

PURPOSE: Local recurrence occurs in ~ 19% of sinonasal inverted papilloma (SNIP) surgeries and is strongly associated with incomplete resection. During surgery, it is technically challenging to visualize and resect all SNIP tissue in this anatomically complex area. Proteins that are overexpressed in SNIP, such as vascular endothelial growth factor (VEGF), may serve as a target for fluorescence molecular imaging to guide surgical removal of SNIP. A proof-of-concept study was performed to investigate if the VEGF-targeted near-infrared fluorescent tracer bevacizumab-800CW specifically localizes in SNIP and whether it could be used as a clinical tool to guide SNIP surgery. METHODS: In five patients diagnosed with SNIP, 10 mg of bevacizumab-800CW was intravenously administered 3 days prior to surgery. Fluorescence molecular imaging was performed in vivo during surgery and ex vivo during the processing of the surgical specimen. Fluorescence signals were correlated with final histopathology and VEGF-A immunohistochemistry. We introduced a fluorescence grid analysis to assess the fluorescence signal in individual tissue fragments, due to the nature of the surgical procedure (i.e., piecemeal resection) allowing the detection of small SNIP residues and location of the tracer ex vivo. RESULTS: In all patients, fluorescence signal was detected in vivo during endoscopic SNIP surgery. Using ex vivo fluorescence grid analysis, we were able to correlate bevacizumab-800CW fluorescence of individual tissue fragments with final histopathology. Fluorescence grid analysis showed substantial variability in mean fluorescence intensity (FImean), with SNIP tissue showing a median FImean of 77.54 (IQR 50.47-112.30) compared to 35.99 (IQR 21.48-57.81) in uninvolved tissue (p < 0.0001), although the diagnostic ability was limited with an area under the curve of 0.78. CONCLUSIONS: A fluorescence grid analysis could serve as a valid method to evaluate fluorescence molecular imaging in piecemeal surgeries. As such, although substantial differences were observed in fluorescence intensities, VEGF-A may not be the ideal target for SNIP surgery. TRIAL REGISTRATION: NCT03925285.

The inactivated infectious bronchitis virus (IBV) vaccine used as booster in layer hens influences the breadth of protection against challenge with IBV variants.

To achieve long term protection of laying and breeding hens against aberrant egg production caused by infectious bronchitis virus (IBV), a vaccination programme incorporating both live-attenuated and inactivated IBV vaccines is required. High quality IBV vaccines of both types are widely available, but the number of IBV variants of global importance continues to increase and it is not possible to develop vaccines against each one of them. Therefore, it is desirable to perform studies under controlled conditions to determine which IBV vaccine(s) provide the best protection for laying hens against different IBV challenges. Previous vaccination and challenge studies have shown that it is possible to obtain relevant data in a small number of laying hens housed under conditions of strict isolation. The present work extends this finding by investigating the efficacy, against challenge with five IBV strains of global importance, of an IBV vaccination programme including two live-attenuated IBV vaccines (Massachusetts and 793B types) and three different commercially available inactivated vaccines each containing antigen against at least one IBV strain. The results reported here confirm the importance of IBV vaccination for laying hens, show that efficient live priming makes a beneficial contribution to this protection and confirm that inactivated IBV vaccines contribute significantly to effective protection against at least the five IBV challenge strains used here. Furthermore, we provide data to support the "protectotype concept", long-established using different live-attenuated IBV vaccines in young chickens, is valid in broadening protection against IBV challenges in laying birds.RESEARCH HIGHLIGHTSIBV vaccination is essential as an aid in protecting laying hens against IBV infection.Live priming is a beneficial part of the IBV vaccination programme.IBV inactivated vaccine improves IBV protection.Heterologous IBV protection is confirmed in laying hens.

Colorectal anastomotic leak: transcriptomic profile analysis.

BACKGROUND: Anastomotic leakage in patients undergoing colorectal surgery is associated with morbidity and mortality. Although multiple risk factors have been identified, the underlying mechanisms are mainly unknown. The aim of this study was to perform a transcriptome analysis of genes underlying the development of anastomotic leakage. METHODS: A set of human samples from the anastomotic site collected during stapled colorectal anastomosis were used in the study. Transcriptomic profiles were generated for patients who developing anastomotic leakage and case-matched controls with normal anastomotic healing to identify genes and biological processes associated with the development of anastomotic leakage. RESULTS: The analysis included 22 patients with and 69 without anastomotic leakage. Differential expression analysis showed that 44 genes had adjusted P < 0.050, consisting of two upregulated and 42 downregulated genes. Co-functionality analysis of the 150 most upregulated and 150 most downregulated genes using the GenetICA framework showed formation of clusters of genes with different enrichment for biological pathways. The enriched pathways for the downregulated genes are involved in immune response, angiogenesis, protein metabolism, and collagen cross-linking. The enriched pathways for upregulated genes are involved in cell division. CONCLUSION: These data indicate that patients who develop anastomotic leakage start the healing process with an error at the level of gene regulation at the time of surgery. Despite normal macroscopic appearance during surgery, the transcriptome data identified several differences in gene expression between patients who developed anastomotic leakage and those who did not. The expressed genes and enriched processes are involved in the different stages of wound healing. These provide therapeutic and diagnostic targets for patients at risk of anastomotic leakage.

Decrease of Mycoplasma gallisepticum seroprevalence and introduction of new genotypes in Dutch commercial poultry during the years 2001-2018.

Almost two decades ago, in addition to a compulsory M. gallisepticum (Mg) monitoring programme of breeding stock based on European Union regulations, the Dutch poultry industry added national regulations to further reduce the Mg prevalence in Dutch commercial poultry. Currently, all commercial chicken and turkey flocks except broilers are monitored for Mg. All breeding flocks on a farm where one or more flocks tested Mg positive are culled. Mg positive layer pullets are channelled and layer pullets placed on Mg positive multi-age farms are vaccinated. The monitoring data obtained were analysed covering a period of 17 years. Moreover, 31 Dutch Mg isolates from the same period were analysed by multilocus sequence typing (MLST) and compared to available PubMLST data. The results show that in breeding stock the seroprevalence decreased from 1.6% to 0.0%, in commercial layers from 6.3% to 1.9%, and in meat turkeys from 17.6% to 2.4%. The MLST results showed the presence of closely related and identical sequence types (STs) within the different Dutch poultry types. Similar STs were found in Northern and Southern Europe only. The results show a fast decline in the Mg prevalence since 2001, although in layers the Mg prevalence has stabilized and suggests backyard poultry might pose a risk for commercial poultry. The need for Mg control across poultry sectors and in trade was confirmed by the similarity in STs found in different types of poultry and regions. These results from the Dutch poultry industry can be extrapolated to Mg control in general.

In ovo application of a live infectious bursal disease vaccine to commercial broilers confers proper immunity.

Infectious bursal disease (IBD) is an economically important disease of young chickens caused by the Avibirnavirus infectious bursal disease virus (IBDV). Besides biosecurity, vaccination is the most important measure for IBDV control. Sufficient levels of maternally derived antibodies (MDA) protect against early challenge and also interfere with the take of live conventional vaccines. Recently, the field surveys conducted in four countries, published by Ashash, U., Noach, C., Perelman, B., Costello, C., Sansalone, P., Brazil, T. & Raviv, Z. [(2019). In ovo and day of hatch application of a live infectious bursal disease virus vaccine to commercial broilers. Avian Diseases, 63, 713-720] using the MB-1 vaccine strain by in ovo application or sub-cutaneous route at the day of hatch seem to conflict with the rule that very early application of a conventional live vaccine in birds with significant levels of MDA has very little chance of a successful immune response. An in ovo vaccination-challenge controlled experiment with MB-1 vaccine was performed using commercial broilers with high levels of MDA against IBDV and a vvIBDV challenge at 22 or 36 days of age. Clinical signs, bursa-bodyweight ratios, histology, serology, RT-PCR, Sanger- and deep sequencing were used to study the efficacy and safety of the in ovo-applied MB1 vaccine in comparison to an established immuno-complex vaccine. The study findings confirmed that the in ovo application of the live MB-1 vaccine in commercial broilers was successful and induced full protection against a vvIBDV challenge at 22 and 36 days of age, demonstrated by the bursa lesion score and qPCR and IBDV genotyping. Comparable to the field studies, a delayed viral replication of 2-3 weeks, following the in ovo administration of the MB1 vaccine, was observed.

A serological divide: men who have sex with men's attitudes on HIV risk reduction strategies.

The expanding HIV risk reduction toolkit increases options for men who have sex men (MSM), but increasing options in combination with different preferences may complicate promoting risk reduction. To investigate what strategies MSM prefer, data of 3310 participants in the online survey "Men & Sexuality" (Median age = 37 years, 320 (9.7%) HIV positive) was analysed. Questions assessed attitudes towards HIV risk reduction strategies. Participants had the most positive attitudes regarding PrEP and HIV testing, while withdrawal and strategic positioning were least preferred (all p's < .001). Condoms were seen as acceptable to partners and effective but scored low on sexual pleasure. HIV-positive participants were more negative about condoms and more positive about viral load sorting than HIV-negative participants (F(12,3297) = 5.09, p < .001, [Formula: see text] = .02). Findings highlight a preference for HIV risk reduction strategies (PrEP and HIV testing) that do not diminish sexual pleasure and can be applied independent of sexual partners. A serological divide was apparent: HIV-negative MSM were less negative about condoms than HIV-positive MSM, suggesting that condom promotion remains a viable strategy for HIV-negative MSM. Taken together, results indicate a need for personalized approaches to the promotion of HIV risk reduction strategies, accounting for individual preferences and strategy effectiveness.

Reducing health disparities: key factors for successful implementation of social network testing with HIV self-tests among men who have sex with men with a non-western migration background in the Netherlands.

Improving testing uptake among men who have sex with men with a non-western migration background (MSM-NW) is a public health priority, as people who are unaware of their HIV infection are at higher risk of transmitting HIV and are unable to benefit from HIV treatment. Formative semi-structured interviews with 13 MSM-NW assessed key factors for the successful implementation of social network testing with HIV self-tests (SNT-HIVST). Interviews were thematically analysed. Participants mentioned that SNT-HIVST might overcome barriers to regular HIV testing including; being seen while testing, disclosure of sexual identity, and stigma related to HIV and sexual practices. Trust between the HIVST distributer and receiver was important. Finally, SNT-HIVST requires tailored peer support to address practical, informational, and emotional needs. MSM-NW distributing HIVST can have an important role in reducing health disparities in testing uptake among MSM-NW. Provided sufficient trust among MSM-NW; key factors found for successful implementation were education through an e-tool, and establishing quality support by a peer-coordinator for unanticipated questions. In conclusion, HIVST distribution has the potential to reduce health disparities in testing uptake, in particular, if adjusted to MSM-NWs individual preferences and the needs and preferences of the person they are inviting to test.

Relative contribution of vertical, within-farm and between-farm transmission of Mycoplasma synoviae in layer pullet flocks.

In this study, the relative contribution of vertical transmission, within-farm transmission and between-farm transmission of Mycoplasma synoviae in layer pullet flocks was quantified using logistic regression analysis. Data from 311 Dutch pullet flocks, of which 172 (55%) were positive for M. synoviae, were included in the study. Also the M. synoviae status of the parent stock of these flocks was included. The M. synoviae status was determined with the M. synoviae rapid plate agglutination test. Data analysis showed that vertical transmission was the most important transmission route for M. synoviae in layers as is demonstrated by an odds ratio of 5.8 (P = 0.000). A positive association with M. synoviae infections was found for layer pullet flocks on a multi-house farm where at least one other flock was M. synoviae-positive compared to single-house farms (odds ratio 3.1, P = 0.022), while a negative association was found when no other M. synoviae-positive flocks were present (odds ratio = 0.2, P = 0.003). No association was found between M. synoviae status of pullet flocks and poultry farm density. Odds ratios were 0.54 (P = 0.288) and 0.34 (P = 0.073), respectively, for medium and highest poultry farm density compared to lowest poultry farm density. This is the first time that the relative contribution of horizontal and vertical transmission of M. synoviae has been quantified. These results can be extrapolated to M. synoviae control in general, and emphasize the importance of M. synoviae control in parent stock and practical channelling.

Characterization of infectious bronchitis virus D181, a new serotype (GII-2).

This paper describes the characterization of a new infectious bronchitis virus (IBV) strain D181, that rapidly evolved from a low-level incidental finding in 2017 to become the second most isolated IBV strain in Dutch layers and breeders in 2018, as well as being found in samples from Germany and Belgium. Based on the sequence of the S gene and the results of cross-neutralization tests, D181 can be considered as a new serotype and the second lineage within genotype II (GII-2). The experimental infection of SPF hens confirmed the ability of D181 to cause a drop in egg production, and immunohistochemistry showed presence of the virus in the trachea, lung and conjunctiva at 5 days post inoculation and in the caecal tonsils at 5 and 8 days post inoculation. In silico analysis of several widely used PCR primers indicated that primer sets adapted for GII might be needed to detect D181, as many general S1 primers might miss it.

Spotlight on avian coronaviruses.

Coronaviruses (CoVs) mainly cause enteric and/or respiratory signs. Mammalian CoVs including COVID-19 (now officially named SARS-CoV-2) belong to either the Alphacoronavirus or Betacoronavirus genera. In birds, the majority of the known CoVs belong to the Gammacoronavirus genus, whilst a small number are classified as Deltacoronaviruses. Gammacoronaviruses continue to be reported in an increasing number of avian species, generally by detection of viral RNA. Apart from infectious bronchitis virus in chickens, the only avian species in which CoV has been definitively associated with disease are the turkey, pheasant and guinea fowl. Whilst there is strong evidence for recombination between gammacoronaviruses of different avian species, and between betacoronaviruses in different mammals, evidence of recombination between coronaviruses of different genera is lacking. Furthermore, the recombination of an alpha or betacoronavirus with a gammacoronavirus is extremely unlikely. For recombination to happen, the two viruses would need to be present in the same cell of the same animal at the same time, a highly unlikely scenario as they cannot replicate in the same host!

Effect of IBV D1466 on egg production and egg quality and the effect of heterologous priming to increase the efficacy of an inactivated IBV vaccine.

To protect layers, breeders and grandparents against damage by infectious bronchitis virus infections during the laying period, vaccination using live priming followed by a boost with inactivated IB vaccine is commonly used. For many IB variants, homologous live vaccines are not available for priming. Very little is known about the efficacy of priming with heterologous live IB vaccines (or combination of live IB vaccines) to induce broad IB protection in long-living chickens. In this study, the protection levels induced by vaccination programmes with only heterologous live priming by a Massachusetts vaccine and a 4/91 vaccine, only a multivalent inactivated vaccine that contained D1466 antigen and a combination of both, against a D1466 challenge were compared. The infection with infectious bronchitis virus D1466, a genotype II, lineage 1 virus, was able to cause serious damage to the unvaccinated laying hens resulting in respiratory signs, a long-lasting drop in egg production and loss of egg quality. All three vaccination programmes induced significant levels of protection against challenge with a pathogenic D1466 strain. Overall, the vaccination programme using the broad heterologous live priming and the inactivated vaccine provided high protection against the combination of egg drop and loss of egg quality. The results showed that this combination of heterologous live vaccines was able to increase the efficacy of the inactivated infectious bronchitis virus vaccine despite the very low antigenic relationship of both live vaccines with the challenge strain.

Major difference in clinical outcome and replication of a H3N1 avian influenza strain in young pullets and adult layers.

In this study, we investigated the pathogenicity, replication and tropism of the low pathogenic avian influenza (LPAI) strain A/chicken/Belgium/460/2019(H3N1) in adult SPF layers and young SPF males. The inoculated hens showed 58% mortality and a 100% drop in egg production in the second week post inoculation. The high viral loads in the cloacal samples coincided with the period of the positive immunohistochemistry of the oviduct, acute peritonitis and time of mortality, suggesting that the replication of H3N1 in the oviduct was a major component of the onset of clinical disease and increased level of excretion of the virus. In the inoculated young birds, the clinical signs were very mild with the exception of one bird. The results suggest that the time of replication of the virus was much shorter than in the adult layers; some of the young males did not show any proof of being infected at all. To conclude, the results of the study in young birds confirmed the intravenous pathogenicity test results but also showed that the clinical signs in adult layers were very severe. Based on the mortality without a bacterial component, complete drop of egg production and post mortem findings, this H3N1 strain is a moderately virulent strain, the highest category for LPAI strains. It is important to realize that if HPAI did not exist, this moderately virulent H3N1 virus would most likely to be considered as a very virulent virus.

Factors associated with self-reported hepatitis B virus vaccination status among men who have sex with men in the Netherlands.

Background Reducing the number of new acute hepatitis B virus (HBV) infections to zero by 2022 is an important goal in the Netherlands. Free HBV vaccination is available for population groups at higher risk of infection, including men who have sex with men (MSM). Identifying correlates of HBV vaccination among MSM can guide the development of health promotion interventions to increase coverage of HBV vaccination. METHODS: We assessed factors associated with the HBV vaccination status of 4270 MSM in the Netherlands. Data were collected through the 2018 online Men & Sexuality survey. RESULTS: Multinomial regression analysis showed that lower education level, having never tested for HIV, not recently diagnosed with a sexually transmissible infection, recently having had sex abroad and unknown HBV testing status were associated with higher odds of being unvaccinated as opposed to fully vaccinated. Living in Amsterdam and testing HBV negative were associated with lower odds of being unvaccinated as opposed to fully vaccinated. Age (25-39 years vs younger ages), living in Amsterdam and using pre-exposure prophylaxis decreased the odds to be partly vaccinated as opposed to fully vaccinated; having a migration background increased these odds. CONCLUSIONS: HBV vaccination rates among MSM will not reduce HBV transmission to zero. HBV promotion should focus on MSM outside of Amsterdam who are likely less connected with sexual health services and may be at lower (perceived) risk. The factors identified related to HBV vaccination status provide guidance for health promotion interventions to increase uptake and vaccination completion among MSM.

Spotlight on avian pathology: infectious bronchitis virus.

Infectious bronchitis is a highly infectious disease of the domestic chicken of all ages and type, affecting the respiratory, renal and reproductive systems. Secondary bacterial infections are common and have a serious economic and welfare impact. Many genotypic and serotypic variants of infectious bronchitis virus (IBV) exist worldwide, making diagnosis difficult, and challenging control strategies. Vaccination, requiring the use of both live-attenuated and inactivated vaccines, is needed to control IBV infections; to date, attempts to develop vectored vaccines as effective as the traditional vaccines have been unsuccessful.

Induction of IBV strain-specific neutralizing antibodies and broad spectrum protection in layer pullets primed with IBV Massachusetts (Mass) and 793B vaccines prior to injection of inactivated vaccine containing Mass antigen.

In an initial study in specified pathogen free (SPF) chickens, a heterologous virus neutralizing (VN) antibody response to IBV variants Q1, Variant 2 (Var 2), D388/QX (D388), D274 and Arkansas (DPI) was observed using a vaccination programme incorporating two different live-attenuated IBV vaccines, followed by boosting with an inactivated vaccine containing IBV Massachusetts (Mass) antigen. Therefore, a more detailed study was undertaken in SPF layer-type chickens primed with IBV Mass and 793B vaccines. The efficacy of single or repeated vaccination with a multivalent inactivated vaccine containing IBV antigen was determined against challenge with five virulent IBVs: Mass (M41), 793B (4/91), D388, Q1 and Var 2. The parameters assessed were serological response, respiratory signs, egg production, post mortem abnormalities in the reproductive organs and abdomen, and incidence of IBV antigen in kidneys. Increased VN titres were recorded against the five IBV challenge strains, with a significantly higher level of protection against drops in egg production following challenge. The difference between one or two vaccinations with inactivated vaccine was not significant in terms of egg production. However, a significantly increased level of protection was seen in the lower percentage of hens with free yolk in the abdomen and/or peritonitis post challenge with IBV variants, D388, Q1 and Var 2 not included in the vaccination programme. A lower incidence of acute, degenerated ovaries was found in groups given one injection of inactivated vaccine following live priming, and this was significantly lower than in groups given only live priming.

The prevalence of antibody responses against Staphylococcus aureus antigens in patients with atopic dermatitis: a systematic review and meta-analysis.

BACKGROUND: Staphylococcus aureus plays a role in the pathogenesis of atopic dermatitis (AD), possibly via the expression of various virulence antigens. An altered antibody response towards these antigens might contribute to inflammation. OBJECTIVES: To provide an overview of the varying prevalences and odds of antibody responses against S. aureus antigens in patients with AD. METHODS: Data were systematically obtained from Embase, MEDLINE, Web of Science, Scopus, Cochrane, PubMed and Google Scholar up to 12 February 2016. We selected all original observational and experimental studies assessing antistaphylococcal antibodies in serum of patients with AD. Prevalences and odds ratios (ORs) of IgE, IgG, IgM and IgA against S. aureus in patients with AD vs. healthy controls were pooled using the random-effects model. We calculated I2 statistics to assess heterogeneity and rated study quality using the Newcastle-Ottawa Scale. RESULTS: Twenty-six articles (2369 patients) were included, of which 10 were controlled studies. Study quality was fair to poor. Patients with AD had higher prevalences of IgE against staphylococcal enterotoxin (SE)A (OR 8·37, 95% confidence interval 2·93-23·92) and SEB (OR 9·34, 95% confidence interval 3·54-24·93) compared with controls. Prevalences of antistaphylococcal IgE were 33% for SEA, 35% for SEB and 16% for toxic shock syndrome toxin-1. However, study heterogeneity and imprecision should be taken into consideration when interpreting the results. Data on IgG, IgM and IgA, as well as other antigens, are limited. CONCLUSIONS: Patients with AD more often show an IgE antibody response directed against S. aureus superantigens than healthy controls, supporting a role for S. aureus in AD pathogenesis.

IgG response against Staphylococcus aureus is associated with severe atopic dermatitis in children.

BACKGROUND: An altered immune response against Staphylococcus aureus might contribute to inflammation and barrier damage in atopic dermatitis (AD). OBJECTIVES: To profile IgG antibodies against 55 S. aureus antigens in sera of children with mild-to-severe AD and to evaluate the association between IgG levels and disease severity. METHODS: In this cross-sectional study, we included children with AD from two interventional study cohorts, the Shared Medical Appointment (SMA) cohort (n = 131) and the older DAVOS cohort (n = 76). AD severity was assessed using the Self-Administered Eczema Area and Severity Index (SA-EASI) and levels of thymus and activation-regulated chemokine (TARC) in serum. IgG antibody levels against 55 S. aureus antigens were quantified simultaneously using a Luminex assay. Pair-wise correlations were calculated between the 55 IgG levels using the Spearman rank correlation test. Linear regression analysis was performed to test for associations between 55 IgG levels and SA-EASI and TARC, adjusting for age, sex and S. aureus colonization. RESULTS: In the SMA cohort, 16 antigens were associated with SA-EASI and 12 with TARC (10 overlapping antigens; P-values 0·001-0·044). The associated IgG antibodies targeted mainly secreted proteins with immunomodulatory functions. In the DAVOS study, IgG levels against only four and one S. aureus antigen(s) were associated with SA-EASI and TARC, respectively (no overlap). CONCLUSIONS: In young children, severity of AD is associated with an IgG response directed against S. aureus antigens with mainly immunomodulatory functions. These findings encourage further evaluation of the role of S. aureus in the pathogenesis of AD.