Leishmania infantum and Dirofilaria immitis infections in Italy, 2009-2019: Changing distribution patterns

Background: For long time, canine leishmaniosis (CanL) was considered endemic in the southern, central, and insular regions of Italy, whereas heartworm disease (HW) caused by Dirofilaria immitis was considered endemic in the northern region and in the swampy Po Valley. Following the reports of new foci of both diseases, in this study we update the distribution patterns and occurrence of new foci of CanL and HW discussing the main drivers for the changes in the epidemiology of these two important zoonotic canine vector-borne diseases. Methods: Based on the statistical analyses of serological assays (n = 90,633) on L. infantum exposure and D. immitis infection performed by two reference diagnostic centres in Italy over a ten-year period (2009-2019) irrespective of the anamnesis of dogs. The distribution patterns of both parasites are herein presented along with the occurrence of new foci. Results: Results highlighted the changing distribution patterns of L. infantum vs D. immitis infection in Italy. CanL is endemic in some areas of northern regions and HW has endemic foci in central and southern regions and islands. Significant differences in L. infantum exposure and HW infection prevalence among the study macroareas were detected. The overall results of the positive tested samples were 28.2% in southern Italy and islands, 29.6% in central Italy and 21.6% in northern Italy for L. infantum and 2.83% in northern Italy, 7.75% in central Italy and 4.97% in southern Italy and islands for HW. HW positivity significantly varied over years (χ 2 = 108.401, df = 10, P < 0.0001), gradually increasing from 0.77% in 2009 to 8.47% in 2016-2017. Conclusions: New potential epidemiological scenarios are discussed according to a range of factors (e.g. environmental modifications, occurrence of competent insect vectors, transportation of infected animals to non-endemic areas, chemoprophylaxis or vector preventative measures), which may affect the current distribution. Overall, the results advocate for epidemiological surveillance programmes, more focussed preventative and control measures even in areas where few or no cases of both diseases have been diagnosed.[Figure not available: see fulltext.

Acute febrile illness is associated with Rickettsia spp infection in dogs

BACKGROUND: Rickettsia conorii is transmitted by Rhipicephalus sanguineus ticks and causes Mediterranean Spotted Fever (MSF) in humans. Although dogs are considered the natural host of the vector, the clinical and epidemiological significance of R. conorii infection in dogs remains unclear. The aim of this prospective study was to investigate whether Rickettsia infection causes febrile illness in dogs living in areas endemic for human MSF. METHODS: Dogs from southern Italy with acute fever (n = 99) were compared with case–control dogs with normal body temperatures (n = 72). Serology and real-time PCR were performed for Rickettsia spp., Ehrlichia canis, Anaplasma phagocytophilum/A. platys and Leishmania infantum. Conventional PCR was performed for Babesia spp. and Hepatozoon spp. Acute and convalescent antibodies to R. conorii, E. canis and A. phagocytophilum were determined. RESULTS: The seroprevalence rates at first visit for R. conorii, E. canis, A. phagocytophilum and L. infantum were 44.8%, 48.5%, 37.8% and 17.6%, respectively. The seroconversion rates for R. conorii, E. canis and A. phagocytophilum were 20.7%, 14.3% and 8.8%, respectively. The molecular positive rates at first visit for Rickettsia spp., E. canis, A. phagocytophilum, A. platys, L. infantum, Babesia spp. and Hepatozoon spp. were 1.8%, 4.1%, 0%, 2.3%, 11.1%, 2.3% and 0.6%, respectively. Positive PCR for E. canis (7%), Rickettsia spp. (3%), Babesia spp. (4.0%) and Hepatozoon spp. (1.0%) were found only in febrile dogs. The DNA sequences obtained from Rickettsia and Babesia PCRs positive samples were 100% identical to the R. conorii and Babesia vogeli sequences in GenBank®, respectively. Febrile illness was statistically associated with acute and convalescent positive R. conorii antibodies, seroconversion to R. conorii, E. canis positive PCR, and positivity to any tick pathogen PCRs. Fourteen febrile dogs (31.8%) were diagnosed with Rickettsia spp. infection based on seroconversion and/or PCR while only six afebrile dogs (12.5%) seroconverted (P = 0.0248). The most common clinical findings of dogs with Rickettsia infection diagnosed by seroconversion and/or PCR were fever, myalgia, lameness, elevation of C-reactive protein, thrombocytopenia and hypoalbuminemia. CONCLUSIONS: This study demonstrates acute febrile illness associated with Rickettsia infection in dogs living in endemic areas of human MSF based on seroconversion alone or in combination with PCR

Frequency of DEA 1 antigen in 1037 mongrel and PUREBREED dogs in Italy

Background: The prevalence of dog erythrocyte antigen (DEA 1) in canine population is approximately 40\u201360%. Often data are limited to a small number of breeds and/or dogs. The aims of this study were to evaluate frequency of DEA 1 in a large population of purebred and mongrel dogs including Italian native breeds and to recognize a possible association between DEA 1 and breed, sex, and genetic and phenotypical/functional classifications of breeds. Frequencies of DEA 1 blood group collected from screened/enrolled blood donors and from healthy and sick dogs were retrospectively evaluated. The breed and the sex were recorded when available. DEA 1 blood typing was assessed by immunocromatographic test on K3EDTA blood samples. The prevalence of DEA 1 antigen was statistically related to breed, gender, F\ue9d\ue9ration Cynologique Internationale (FCI) and genotypic grouping. Results: Sixty-two per cent dogs resulted DEA 1+ and 38% DEA 1-. DEA 1- was statistically associated with Dogo Argentino, Dobermann, German Shepherd, Boxer, Corso dogs, the molossian dogs, the FCI group 1, 2 and 3 and the genetic groups \u201cworking dogs\u201d and \u201cmastiff\u201d. DEA 1+ was statistically associated with Rottweiler, Briquet Griffon Vend\ue9en, Bernese mountain dog, Golden Retriever, the hunting breeds, the FCI group 4, 6, 7 and 8 and the genetic groups \u201cscent hounds\u201d and \u201cretrievers\u201d. No gender association was observed. Conclusions: Data obtained by this work may be clinically useful to drive blood donor enrollment and selection among different breeds

Detection of Leishmania infantum DNA mainly in Rhipicephalus sanguineus male ticks removed from dogs living in endemic areas of canine leishmaniosis

Background: Sand flies are the only biologically adapted vectors of Leishmania parasites, however, a possible role in the transmission of Leishmania has been proposed for other hematophagous ectoparasites such as ticks. In order to evaluate natural infection by Leishmania infantum in Rhipicephalus sanguineus ticks, taking into account its close association with dogs, 128 adult R. sanguineus ticks removed from 41 dogs living in endemic areas of canine leishmaniosis were studied. Methods: Individual DNA extraction was performed from each tick and whole blood taken from dogs. Dog sera were tested for IgG antibodies to L. infantum antigen by ELISA and L. infantum real-time PCR was performed from canine whole blood samples and ticks. Results: Leishmania infantum PCR was positive in 13 ticks (10.1%) including one female, (2.0%) and 12 males (15.2%), and in only five dogs (12.2%). Male ticks had a significantly higher infection rate when compared to female R. sanguineus. The percentage of L. infantum seroreactive dogs was 19.5%. All but two PCR positive dogs were seroreactive. Leishmania infantum PCR positive ticks were removed from seropositive and seronegative dogs with a variety of PCR results. Conclusions: This study demonstrates high prevalence of L. infantum DNA in R. sanguineus ticks removed from L. infantum seropositive and seronegative dogs. The presence of L. infantum DNA was detected mainly in male ticks possibly due to their ability to move between canine hosts and feed on several canine hosts during the adult life stage. Additional studies are needed to further explore the role of R. sanguineus ticks and in particular, male adults, in both the epidemiology and immunology of L. infantum infection in dogs in endemic areas

Multiclass classification of microarray data samples with a reduced number of genes

<p>Abstract</p> <p>Background</p> <p>Multiclass classification of microarray data samples with a reduced number of genes is a rich and challenging problem in Bioinformatics research. The problem gets harder as the number of classes is increased. In addition, the performance of most classifiers is tightly linked to the effectiveness of mandatory gene selection methods. Critical to gene selection is the availability of estimates about the maximum number of genes that can be handled by any classification algorithm. Lack of such estimates may lead to either computationally demanding explorations of a search space with thousands of dimensions or classification models based on gene sets of unrestricted size. In the former case, unbiased but possibly overfitted classification models may arise. In the latter case, biased classification models unable to support statistically significant findings may be obtained.</p> <p>Results</p> <p>A novel bound on the maximum number of genes that can be handled by binary classifiers in binary mediated multiclass classification algorithms of microarray data samples is presented. The bound suggests that high-dimensional binary output domains might favor the existence of accurate and sparse binary mediated multiclass classifiers for microarray data samples.</p> <p>Conclusions</p> <p>A comprehensive experimental work shows that the bound is indeed useful to induce accurate and sparse multiclass classifiers for microarray data samples.</p

Functional analysis of multiple genomic signatures demonstrates that classification algorithms choose phenotype-related genes

Gene expression signatures of toxicity and clinical response benefit both safety assessment and clinical practice; however, difficulties in connecting signature genes with the predicted end points have limited their application. The Microarray Quality Control Consortium II (MAQCII) project generated 262 signatures for ten clinical and three toxicological end points from six gene expression data sets, an unprecedented collection of diverse signatures that has permitted a wide-ranging analysis on the nature of such predictive models. A comprehensive analysis of the genes of these signatures and their nonredundant unions using ontology enrichment, biological network building and interactome connectivity analyses demonstrated the link between gene signatures and the biological basis of their predictive power. Different signatures for a given end point were more similar at the level of biological properties and transcriptional control than at the gene level. Signatures tended to be enriched in function and pathway in an end point and model-specific manner, and showed a topological bias for incoming interactions. Importantly, the level of biological similarity between different signatures for a given end point correlated positively with the accuracy of the signature predictions. These findings will aid the understanding, and application of predictive genomic signatures, and support their broader application in predictive medicine

Assessing sources of inconsistencies in genotypes and their effects on genome-wide association studies with HapMap samples

The discordance in results of independent genome-wide association studies (GWAS) indicates the potential for Type I and Type II errors. We assessed the repeatibility of current Affymetrix technologies that support GWAS. Reasonable reproducibility was observed for both raw intensity and the genotypes/copy number variants. We also assessed consistencies between different SNP arrays and between genotype calling algorithms. We observed that the inconsistency in genotypes was generally small at the specimen level. To further examine whether the differences from genotyping and genotype calling are possible sources of variation in GWAS results, an association analysis was applied to compare the associated SNPs. We observed that the inconsistency in genotypes not only propagated to the association analysis, but was amplified in the associated SNPs. Our studies show that inconsistencies between SNP arrays and between genotype calling algorithms are potential sources for the lack of reproducibility in GWAS results

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation

Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in the maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns of DNA methylation or Foxp3 binding sites were associated with Treg-specific gene expression. We found that Treg-specific DNA hypomethylated regions were closely associated with Treg up-regulated transcriptional start site clusters, whereas Foxp3 binding regions had no significant correlation with either up- or down-regulated clusters in nonactivated Treg cells. However, in activated Treg cells, Foxp3 binding regions showed a strong correlation with down-regulated clusters. In accordance with these findings, the above two features of activation-dependent gene regulation in Treg cells tend to occur at different locations in the genome. The results collectively indicate that Treg-specific DNA hypomethylation is instrumental in gene up-regulation in steady state Treg cells, whereas Foxp3 down-regulates the expression of its target genes in activated Treg cells. Thus, the two events seem to play distinct but complementary roles in Treg-specific gene expression