Comirnaty-induced cardiopulmonary distress and other symptoms of complement-mediated pseudo-anaphylaxis in a hyperimmune pig model: Causal role of anti-PEG antibodies.

Background: Comirnaty, Pfizer-BioNTech's polyethylene-glycol (PEG)-containing Covid-19 vaccine, can cause hypersensitivity reactions (HSRs), or rarely, life-threatening anaphylaxis in a small fraction of immunized people. A causal role of anti-PEG antibodies (Abs) has been proposed, but causality has not yet proven in an animal model. The aim of this study was to provide such evidence using pigs immunized against PEG, which displayed very high levels of anti-PEG antibodies (Abs). We also aimed to find evidence for a role of complement activation and thromboxane A2 release in blood to explore the mechanism of anaphylaxis. Methods: Pigs (n = 6) were immunized with 0.1 mg/kg PEGylated liposome (Doxebo) i.v., and the rise of anti-PEG IgG and IgM were measured in serial blood samples with ELISA. After âˆ¼2-3 weeks the animals were injected i.v. with 1/3 human dose of the PEGylated mRNA vaccine, Comirnaty, and the hemodynamic (PAP, SAP) cardiopulmonary (HR, EtCO2,), hematological (WBC, granulocyte, lymphocyte and platelet counts) parameters and blood immune mediators (anti-PEG IgM and IgG antibodies, thromboxane B2, C3a) were measured as endpoints of HSRs (anaphylaxis). Results: The level of anti-PEG IgM and IgG rose 5-10-thousand-fold in all of 6 pigs immunized with Doxebo by day 6, after which time all animals developed anaphylactic shock to i.v. injection of 1/3 human dose of Comirnaty. The reaction, starting within 1 min involved maximal pulmonary hypertension and decreased systemic pulse pressure amplitude, tachycardia, granulo- and thrombocytopenia, and skin reactions (flushing or rash). These physiological changes or their absence were paralleled by C3a and TXB2 rises in blood. Conclusions: Consistent with previous studies, these data show a causal role of anti-PEG Abs in the anaphylaxis to Comirnaty, which involves complement activation, and, hence, it represents C activation-related pseudo-anaphylaxis. The setup provides the first large-animal model for mRNA-vaccine-induced anaphylaxis in humans.

Exploring the interplay between the core microbiota, physicochemical factors, agrobiochemical cycles in the soil of the historic tokaj mád wine region.

A Hungarian survey of Tokaj-Mád vineyards was conducted. Shotgun metabarcoding was applied to decipher the microbial-terroir. The results of 60 soil samples showed that there were three dominant fungal phyla, Ascomycota 66.36% ± 15.26%, Basidiomycota 18.78% ± 14.90%, Mucoromycota 11.89% ± 8.99%, representing 97% of operational taxonomic units (OTUs). Mutual interactions between microbiota diversity and soil physicochemical parameters were revealed. Principal component analysis showed descriptive clustering patterns of microbial taxonomy and resistance gene profiles in the case of the four historic vineyards (Szent Tamás, Király, Betsek, Nyúlászó). Linear discriminant analysis effect size was performed, revealing pronounced shifts in community taxonomy based on soil physicochemical properties. Twelve clades exhibited the most significant shifts (LDA > 4.0), including the phyla Verrucomicrobia, Bacteroidetes, Chloroflexi, and Rokubacteria, the classes Acidobacteria, Deltaproteobacteria, Gemmatimonadetes, and Betaproteobacteria, the order Sphingomonadales, Hypomicrobiales, as well as the family Sphingomonadaceae and the genus Sphingomonas. Three out of the four historic vineyards exhibited the highest occurrences of the bacterial genus Bradyrhizobium, known for its positive influence on plant development and physiology through the secretion of steroid phytohormones. During ripening, the taxonomical composition of the soil fungal microbiota clustered into distinct groups depending on altitude, differences that were not reflected in bacteriomes. Network analyses were performed to unravel changes in fungal interactiomes when comparing postveraison and preharvest samples. In addition to the arbuscular mycorrhiza Glomeraceae, the families Mycosphaerellacae and Rhyzopodaceae and the class Agaricomycetes were found to have important roles in maintaining soil microbial community resilience. Functional metagenomics showed that the soil Na content stimulated several of the microbiota-related agrobiogeochemical cycles, such as nitrogen and sulphur metabolism; steroid, bisphenol, toluene, dioxin and atrazine degradation and the synthesis of folate.

The Effect of Environmental Factors on Mould Counts and AFB1 Toxin Production by Aspergillus flavus in Maize.

The toxins produced by Aspergillus flavus can significantly inhibit the use of maize. As a result of climate change, toxin production is a problem not only in tropical and subtropical areas but in an increasing number of European countries, including Hungary. The effect of meteorological factors and irrigation on mould colonization and aflatoxin B1 (AFB1) mycotoxin production by A. flavus were investigated in natural conditions, as well as the inoculation with a toxigenic isolate in a complex field experiment for three years. As a result of irrigation, the occurrence of fungi increased, and toxin production decreased. The mould count of fungi and toxin accumulation showed differences during the examined growing seasons. The highest AFB1 content was found in 2021. The main environmental factors in predicting mould count were temperature (Tavg, Tmax ≥ 30 °C, Tmax ≥ 32 °C, Tmax ≥ 35 °C) and atmospheric drought (RHmin ≤ 40%). Toxin production was determined by extremely high daily maximum temperatures (Tmax ≥ 35 °C). At natural contamination, the effect of Tmax ≥ 35 °C on AFB1 was maximal (r = 0.560-0.569) in the R4 stage. In the case of artificial inoculation, correlations with environmental factors were stronger (r = 0.665-0.834) during the R2-R6 stages.

A snapshot on Pestivirus A strains occurring in Central Europe.

Seven dairy farms and a beef herd were sampled to reveal the presence of bovine viral diarrhoea viruses (BVDV) in the cattle population and provide information on the occurrence of the different genotypes of the virus in Hungary and Slovakia. Serum and organ samples, lung, and lymph nodes were collected and submitted to serological testing, RT-qPCR, nucleotide sequencing, and virus isolation. The detected viruses belonged to 1b, 1d, and 1f subtypes. No Pestivirus B was found. Serum samples of cows immunized with a live vaccine containing a subtype 1a virus (Oregon C24V) showed cross-neutralizing activity against the selected representative field strains of each subtype. An RT-qPCR, specific for the vaccine strain was developed to differentiate between vaccine and field viruses and was used to evaluate vaccine virus viraemia and shedding. The obtained data provide baseline information on the currently occurring BVDV genotypes in the region and contribute to elaborating efficient control strategies.

A Systematic Review of the Efficacy of Interventions to Control Aflatoxins in the Dairy Production Chain-Feed Production and Animal Feeding Interventions.

The study presents a systematic review of published scientific articles investigating the effects of interventions aiming at aflatoxin reduction at the feed production and animal feeding phases of the milk value chain in order to identify the recent scientific trends and summarize the main findings available in the literature. The review strategy was designed based on the guidance of the systematic review and knowledge synthesis methodology that is applicable in the field of food safety. The Web of Science and EBSCOhost online databases were searched with predefined algorithms. After title and abstract relevance screening and relevance confirmation with full-text screening, 67 studies remained for data extraction, which were included in the review. The most important identified groups of interventions based on their mode of action and place in the technological process are as follows: low-moisture production using preservatives, acidity regulators, adsorbents and various microbiological additives. The results of the listed publications are summarized and compared for all the identified intervention groups. The paper aimed to help feed producers, farmers and relevant stakeholders to get an overview of the most suitable aflatoxin mitigation options, which is extremely important in the near future as climate change will likely be accompanied by elevated mycotoxin levels.

Prevalence of Coxiella burnetii in bovine placentas in Hungary and Slovakia: Detection of a novel sequence type - Short communication.

Cotyledons (n = 167) from 30 Hungarian and 5 Slovakian dairy cattle herds were analysed for Coxiella burnetii by real-time PCR targeting the IS1111 gene. Eighty (88.9%) out of the 90 cotyledons from retained placentas and 31 (40.3%) out of the 77 cotyledons from normally separated placentas tested positive. Seventeen out of the 80 positive samples (21.3%) originating from retained placentas were found to be highly loaded with C. burnetii with a cycle threshold (Ct) value lower than or equal to 27.08, ranging between 11.92 and 27.08. The rest of the positive samples from retained fetal membranes and from normally separated placentas were moderately loaded with C. burnetii DNA. Five out of the ten samples showing the strongest positivity (Ct 11.92-18.28) from retained placentas were genotyped by multispacer sequence typing based on ten loci, which revealed sequence type (ST) 61, a type that had not been detected in Hungary and Slovakia previously. Retained placenta was more likely in cows with C. burnetii PCR-positive cotyledons (odds ratio: 12.61, P = 0.0023). The high C. burnetii DNA load found in retained fetal membranes may be a potential risk factor for human infection and may also be associated with the retention of fetal membranes.

Serological survey of Coxiella burnetii infections in dairy cattle, sheep, goats and zoo animals in Hungary - Short communication.

Q fever is a disease of high zoonotic potential, but interest in its causative agent is rather low although it causes some public health problems in Hungary. The prevalence of Q fever is highly variable by country. The main reservoirs of the disease are the same domestic ruminant species everywhere, but the epidemiological profile depends on the features of the specific reservoir. The aim of this large-scale study was to demonstrate the importance of Q fever in different species as a possible source for human infection in most regions of Hungary. A total of 851 serum samples from 44 dairy farms, 16 sheep flocks, 4 goat farms and 3 zoos located in different parts of Hungary were tested. The presence of antibodies to Coxiella burnetii was surveyed in dairy cattle (n = 547), goats (n = 71), sheep (n = 200) and zoo animals (n = 33). The animal species tested in Hungary showed different seroprevalence values of C. burnetii infection. Seropositivity by the enzyme-linked immunosorbent assay was found in 258 out of 547 (47.2%) cows and in 69 out of 271 (25.5%) small ruminants, among them in 47 out of 200 (23.5%) sheep and in 22 out of 71 (31.0%) goats. Antibodies to C. burnetii were not detected in zoo animals. Seropositivity was demonstrated in 44 out of 44 (100%) dairy cattle farms, with at least one serum sample found to be positive on each farm. The seropositivity rate of small ruminant farms was 55.0% (11 positive out of 20 tested), with 9 out of 16 (56.3%) sheep flocks and 2 out of 4 (50.0%) goat herds showing seropositivity.

Industrial Dairy Cattle Farms in Hungary Source of Coxiella burnetii Infection in Humans.

Previous research has demonstrated a high prevalence of Coxiella burnetii in the bulk tank milk on large industrial dairy farms of the central and eastern European region. The aim of this survey was to estimate the prevalence of specific IgG antibodies to C. burnetii proving previous infection among dairy farm workers and to determine the possible risk factors. Serum samples from veterinarians, inseminators, animal caretakers, milking parlor workers, and herd managers working on dairy farms were tested for the presence of IgG to phase I and phase II of C. burnetii using an indirect microimmunofluorescence assay. Antibodies phase II to C. burnetii were detected in 59 out of 70 individuals tested (84.3%). All occupational groups are highly exposed to C. burnetii infection. Veterinarians, inseminators, and animal caretakers had 100% seropositivity rate of phase II, whereas the seropositivity rate found among herd managers and milking parlor workers was 71.4% and 47%, respectively. The findings of this survey suggest that the risk of C. burnetii infection is correlated with cattle density in the large dairy farms and also with occupational groups.

Pre-Harvest Modelling and Mitigation of Aflatoxins in Maize in a Changing Climatic Environment-A Review.

Aflatoxins (AFs) are harmful secondary metabolites produced by various moulds, among which Aspergillus flavus is the major AF-producer fungus. These mycotoxins have carcinogenic or acute toxigenic effects on both humans and food producing animals and, therefore, the health risks and also the potential economic damages mounted by them have led to legal restrictions, and several countries have set maximum allowable limits for AF contaminations in food and feed. While colonization of food and feed and AF production by A. flavus are highly supported by the climatic conditions in tropical and subtropical geographic regions, countries in the temperate climate zones are also increasingly exposed to AF-derived health risks due to climate change. In the present study, we have reviewed the available mathematical models as risk assessment tools to predict the possibility of A. flavus infection and levels of AF contaminations in maize in a changing climatic environment. After highlighting the benefits and possible future improvements of these models, we summarize the current agricultural practices used to prevent or, at least, mitigate the deleterious consequences of AF contaminations.

Serological screening for Coxiella burnetii in the context of early pregnancy loss in dairy cows.

Q fever is one of the commonest infectious diseases worldwide. A Coxiella burnetii prevalence of 97.6% has been found by ELISA and PCR tests of the bulk tank milk in dairy cattle farms of Hungary. The herd- and individual-level seroprevalence rates of C. burnetii in the examined dairy cows and farms have dramatically increased over the past ten years. Three high-producing industrial dairy farms were studied which had previously been found ELISA and PCR positive for C. burnetii by bulk tank milk testing. Coxiella burnetii was detected in 52% of the 321 cows tested by ELISA. Pregnancy loss was detected in 18% of the cows between days 29-35 and days 60-70 of gestation. The study found a higher seropositivity rate (80.5%) in the cows that had lost their pregnancy and a seropositivity of 94.4% in the first-bred cows that had lost their pregnancy at an early stage. The ELISA-positive pregnant and aborted cows were further investigated by the complement fixation test (CFT). In dairy herds an average of 66.6% individual seropositivity was detected by the CFT (Phase II) in previously ELISA-positive animals that had lost their pregnancy and 64.5% in the pregnant animals. A higher (Phase I) seropositivity rate (50.0%) was found in the cows with pregnancy loss than in the pregnant animals (38.5%). The high prevalence of C. burnetii in dairy farms is a major risk factor related to pregnancy loss.

Prevalence of Coxiella burnetii in Central and Eastern European dairy herds.

The aim of the present study was to assess the prevalence of Coxiella burnetii in dairy herds in Central and Eastern European countries based on ELISA and PCR tests. A total of 370 bulk tank milk samples were collected in 2019 originating from Croatia (n = 13), Czech Republic (n = 138), Hungary (n = 126), Serbia (n = 24), Slovakia (n = 53) and Slovenia (n = 16). Prevalence of C. burnetii differed according to the country of origin with Croatia showing 100.00%, the Czech Republic 98.55%, Hungary 97.61%, Serbia 70.83%, Slovakia 90.56% and Slovenia showing 62.50% average percentages of the positive herds. C. burnetii specific ELISA showed 100.00% positivity in all examined countries if herds consisted of equal or above 250 milking cows. The growing number of farms managing large number of animals, where cattle density is high correlates with the increasing prevalence of C. burnetii in the region.