Epidemiology and zoonotic transmission of mcr-positive and carbapenemase-producing Enterobacterales on German turkey farms.

Introduction: The emergence of carbapenem-resistant bacteria causing serious infections may lead to more frequent use of previously abandoned antibiotics like colistin. However, mobile colistin resistance genes (mcr) can jeopardise its effectiveness in both human and veterinary medicine. In Germany, turkeys have been identified as the food-producing animal most likely to harbour mcr-positive colistin-resistant Enterobacterales (mcr-Col-E). Therefore, the aim of the present study was to assess the prevalence of both mcr-Col-E and carbapenemase-producing Enterobacterales (CPE) in German turkey herds and humans in contact with these herds. Methods: In 2018 and 2019, 175 environmental (boot swabs of turkey faeces) and 46 human stool samples were analysed using a combination of enrichment-based culture, PCR, core genome multilocus sequence typing (cgMLST) and plasmid typing. Results: mcr-Col-E were detected in 123 of the 175 turkey farms in this study (70.3%). mcr-Col-E isolates were Escherichia coli (98.4%) and Klebsiella spp. (1.6%). Herds that had been treated with colistin were more likely to harbour mcr-Col-E, with 82.2% compared to 66.2% in untreated herds (p = 0.0298). Prevalence also depended on husbandry, with 7.1% mcr-Col-E in organic farms compared to 74.5% in conventional ones (p < 0.001). In addition, four of the 46 (8.7%) human participants were colonised with mcr-Col-E. mcr-Col-E isolates from stables had minimum inhibitory concentrations (MICs) from 4 to ≥ 32 mg/l, human isolates ranged from 4 to 8 mg/l. cgMLST showed no clonal transmission of isolates. For one farm, plasmid typing revealed great similarities between plasmids from an environmental and a human sample. No CPE were found in turkey herds or humans. Discussion: These findings confirm that mcr-Col-E-prevalence is high in turkey farms, but no evidence of direct zoonotic transmission of clonal mcr-Col-E strains was found. However, the results indicate that plasmids may be transmitted between E. coli isolates from animals and humans.

Investigation and response to a large outbreak of leptospirosis in field workers in Lower Saxony, Germany.

Between June and August 2014, 45 cases of leptospirosis were notified among workers on two strawberry farms in North-West Germany. We describe the characteristics of the outbreak and the actions taken to prevent further cases. The activities of the local, federal and national public health and veterinary authorities included collection of case data, laboratory testing of human specimens and of small mammals trapped on the fields, investigation of weather data, as well as information provided to farmers, field workers, physicians and to the authorities in Poland and Romania. Of the 45 identified cases (median age 22, 60% male), 47% were hospitalized. Characteristic symptoms were fever ≥38.5°C, generalized muscle pain and an increase in renal or liver enzymes. Thirteen cases were laboratory confirmed by serological and/or molecular methods. ELISA tests for Leptospira IgG and IgM-antibodies were positive in those samples taken >5 days after hospitalization. The probable causative agent was identified as Leptospira kirschneri serovar Grippotyphosa. Leptospira-specific DNA was found in kidneys of 67% of 64 trapped small mammals and was further identified as Leptospira kirschneri multi locus sequence type 110. During the estimated time period of human infections, the affected region faced warm weather with heavy rainfalls. The results of this investigation are in accordance with the theory of a chain of infection from mice to field workers during warm and humid weather. In 2015, a campaign was initiated to inform physicians, farmers and workers to enhance prevention measures, such as the use of personal protective equipment and early consultation of physicians in case of illness. Since then, no further outbreak occurred.

[Cooperation and networking in early prevention and intervention and child protection: the importance of evidence-based methods]. / Kooperation und Vernetzung im Bereich Frühe Hilfen und Kinderschutz: Bedeutung evidenzbasierter Methoden.

Prevention, intervention and child protection in early childhood essentially need well-established interdisciplinary systematic networking. Individual, heterogeneous and complex needs of families cannot be met by one profession alone. Successful cooperation of various institutions and professions is based on fixed arrangements and cooperation pathways. Networking has to be systematically established in everyday routine to be able to work in difficult emergency cases of child protection. Only well established cooperation is experienced as a support for the participants of the network and not as an additional complication. Prerequisite for such a development of favorable conditions is an evidence-based knowledge of the impact of different structures of cooperation, relations and conditions. This requires data collection with the aim of further empirically based development of local network structures. Three tools for such surveys have been developed and tested in the field.

Peripheral and central cyclooxygenase (COX) products may contribute to the manifestation of brain-controlled sickness responses during localized inflammation induced by macrophage-activating lipopeptide-2 (MALP-2).

We investigated whether an inflammation-dependent activation of the brain occurs in response to systemic intraperitoneal (i.p.) or local injections of macrophage-activating lipopeptide-2 (MALP-2) into a subcutaneous (s.c.) air pouch, and whether local (peripheral) or central cyclooxygenase (COX)-2-dependent formations of prostaglandin E(2) (PGE(2)) are involved in MALP-2-induced illness responses. Body temperature, activity, food and water intake were measured telemetrically. Local (s.c.) and circulating levels of PGE(2) were measured by an ELISA. Inflammatory activation of the brain in response to MALP-2 was determined by immunohistochemical detection of the transcription factors NFkappaB and STAT3 in cell nuclei as well as the appearance of COX-2 at the same sites. S.c. treatment with the preferential COX-2 inhibitor meloxicam attenuated, but not abolished fever induced by local injections of MALP-2 into the pouch. Local MALP-2-induced formation of PGE(2) was blunted by treatment with meloxicam. In the brain, i.p. stimulation with MALP-2-induced nuclear STAT3- and NFkappaB-translocation in the vasculature and the sensory circumventricular organs, which was accompanied by an increase in COX-2 immunoreactivity (IR) in endothelial cells. Local MALP-2-treatment induced a moderate STAT3 activation and a small but significant increase in COX-2 IR while no NFkappaB-activation could be observed in the brains of these animals. We demonstrated that the activation of the brain STAT3 (NFkappaB)-COX-2 singling cascade seems to be involved in the manifestation of brain-controlled illness symptoms induced by systemic and local inflammatory stimulation with MALP-2. The present data further suggest a contribution of peripherally produced PGE(2) to MALP-2-induced activation of brain sites implicated in fever.

Prefrontal-temporal gray matter deficits in bipolar disorder patients with persecutory delusions.

OBJECTIVES: Although brain structural deficits have been repeatedly associated with bipolar disorder (BD), inconsistency in morphometric results has been a feature of neuroimaging studies. We hypothesize that this discrepancy is related to the heterogeneity of BD, and examine the question of whether or not more homogeneous clinical subgroups display a more coherent pattern of morphometric abnormalities. METHODS: In a case-control design, we examined differences in gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) concentration in 42 BD patients and 42 healthy matched controls using optimized voxel-based morphometry (VBM). Subgroup analyses of patients with a lifetime history of psychotic symptoms (BDP, n=30) and patients with mood-incongruent psychotic symptoms in the form of persecutory delusions (BDPD, n=15) were performed to accord with previous genetic findings. RESULTS: Analysis of the total BD sample was largely inconclusive, but the BDPD patient subgroup displayed a widespread pattern of significant decreases in GM concentration in the dorsolateral prefrontal (DLPFC), temporal and cingulate cortices, and a significant CSF increase in the adjacent outer ventricular sulci. Comparison of BDPD patients versus BD and BDP patients without persecutory delusions revealed a significant GM decrease in the left DLPFC for the former group. CONCLUSIONS: BDPD show pronounced structural abnormalities of the prefrontal and temporal lobes which are similar to the deficits previously reported for schizophrenia (SCZ). Our findings suggest that stratification based solely on psychotic symptoms is insufficient for the differentiation of BD into biologically meaningful subgroups, but also question the pathophysiological validity of the dichotomy in classification between schizophrenia and BD.

Combined effects of exonic polymorphisms in CRHR1 and AVPR1B genes in a case/control study for panic disorder.

Accumulating evidence from animal studies suggests that the corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) neuropeptide systems, contribute to anxiety behavior. To investigate whether polymorphisms in the genes regulating these two systems may alter susceptibility to anxiety disorders in humans, we genotyped 71 single nucleotide polymorphisms (SNPs) in CRH, CRHR1, CRHR2, AVP, AVPR1A, AVPR1B in a German sample from Munich with patients suffering from panic disorder and matched healthy controls (n = 186/n = 299). Significant associations were then replicated in a second German sample with 173 patients with panic disorder and 495 controls. In both samples separately and the combined sample, SNPs within CHRH1 and AVPR1B were nominally associated with panic disorder. We then tested two locus multiplicative and interaction effects of polymorphisms of these two genes on panic disorder. Fifteen SNP pairs showed significant multiplicative effects in both samples. The SNP pair with the most significant association in the combined sample (P = 0.00057), which withstood correction for multiple testing, was rs878886 in CRHR1 and rs28632197 in AVPR1B. Both SNPs are of potential functional relevance as rs878886 is located in the 3' untranslated region of the CRHR1 and rs28632197 leads to an arginine to histidine amino acid exchange at position 364 of AVPR1B which is located in the intracellular C-terminal domain of the receptor. These data suggest that polymorphisms in the AVPR1B and the CRHR1 genes alter the susceptibility to panic disorder.

Macrophage-activating lipopeptide-2 (MALP-2) induces a localized inflammatory response in rats resulting in activation of brain sites implicated in fever.

Macrophage-activating lipopeptide-2 (MALP-2) has been identified as the pathogen-associated molecular pattern of Mycoplasma fermentans, which causes stimulation of the innate immune system through the activation of the heterodimeric Toll-like receptors (TLRs) 2 and 6. Based on the reported protective effects of MALP-2 on healing of skin wounds, the central goal of this study was to evaluate the capacity of MALP-2 to induce a localized inflammatory response in an established model of a subcutaneous air pouch. Injections of MALP-2 into the pouch caused fever and some components of sickness behavior in rats. At the subcutaneous site of localized inflammation, a massive formation of tumor necrosis factor-alpha (TNF), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) could be demonstrated in response to injections of MALP-2. Moderate amounts of IL-6 and PGE2 seemed to enter the systemic circulation of MALP-2-treated rats. The IL-6, which appeared in the blood after injection of MALP-2 into the air pouch was sufficient to cause a direct activation of brain cells in areas which lack a complete blood-brain barrier, namely in the sensory circumventricular organs (sCVOs), the organum vasculosum laminae terminalis (OVLT), the subfornical organ (SFO), and the area postrema (AP). The stimulation of cells at these brain sites was revealed by demonstration of a nuclear translocation of the transcription factor STAT3 (signal transducer and activator of transcription 3). Corresponding to the circulating levels of IL-6, the nuclear STAT3 activation of cells within the sCVOs was much less pronounced after local subcutaneous when compared to systemic treatment with MALP-2. In conclusion, cells within the subcutaneous compartment are activated by the TLR2/6 agonist MALP-2. Fever and sickness behavior induced by injection of MALP-2 into subcutaneous tissue may, in part, be mediated by a spillover of IL-6 from the subcutaneous site of inflammation into the blood to cause activation of brain sites which are implicated in the manifestation of these illness responses.