ABSTRACT
BACKGROUND: The aim of this study was to investigate the relationship between prior Anisakis infections and upper gastrointestinal bleeding (UGIB), and its interaction with non-steroidal anti-inflammatory drug (NSAID) intake. METHODS/PRINCIPAL FINDINGS: We conducted a hospital-based case-control study covering 215 UGIB cases and 650 controls. Odds ratios (ORs) with their confidence intervals (95% CIs) were calculated, as well as the ratio of the combined effects to the sum of the separate effects of Anisakis allergic sensitization and NSAIDs intake. Prior Anisakis infections were revealed by the presence of anti-Anisakis IgE antibodies specific to the recombinant Ani s 1 and Ani s 7 allergens used as the targets in indirect ELISA. Prior Anisakis infections (OR 1.74 [95% CI: 1.10 to 2.75]) and the intake of NSAIDs (OR 6.63 [95% CI: 4.21 to 10.43]) increased the risk of bleeding. Simultaneous NSAIDs intake and Anisakis allergic sensitization increased the risk of UGIB 14-fold (OR=14.46 [95% CI: 6.08 to 34.40]). This interaction was additive, with a synergistic index of 3.01 (95% CI: 1.18-7.71). CONCLUSIONS: Prior Anisakis infection is an independent risk factor for UGIB, and the joint effect with NSAIDs is 3 times higher than the sum of their individual effects.
Subject(s)
Anisakiasis/complications , Anisakis/pathogenicity , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Gastrointestinal Hemorrhage/chemically induced , Hypersensitivity/complications , Aged , Aged, 80 and over , Animals , Anisakiasis/immunology , Anisakis/immunology , Antibodies, Helminth/blood , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Hypersensitivity/immunology , Immunoglobulin E/blood , Male , Middle AgedABSTRACT
Infections caused by human parasites (HPs) affect the poorest 500 million people worldwide but chemotherapy has become expensive, toxic, and/or less effective due to drug resistance. On the other hand, many 3D structures in Protein Data Bank (PDB) remain without function annotation. We need theoretical models to quickly predict biologically relevant Parasite Self Proteins (PSP), which are expressed differentially in a given parasite and are dissimilar to proteins expressed in other parasites and have a high probability to become new vaccines (unique sequence) or drug targets (unique 3D structure). We present herein a model for PSPs in eight different HPs (Ascaris, Entamoeba, Fasciola, Giardia, Leishmania, Plasmodium, Trypanosoma, and Toxoplasma) with 90% accuracy for 15 341 training and validation cases. The model combines protein residue networks, Markov Chain Models (MCM) and Artificial Neural Networks (ANN). The input parameters are the spectral moments of the Markov transition matrix for electrostatic interactions associated with the protein residue complex network calculated with the MARCH-INSIDE software. We implemented this model in a new web-server called MISS-Prot (MARCH-INSIDE Scores for Self-Proteins). MISS-Prot was programmed using PHP/HTML/Python and MARCH-INSIDE routines and is freely available at: . This server is easy to use by non-experts in Bioinformatics who can carry out automatic online upload and prediction with 3D structures deposited at PDB (mode 1). We can also study outcomes of Peptide Mass Fingerprinting (PMFs) and MS/MS for query proteins with unknown 3D structures (mode 2). We illustrated the use of MISS-Prot in experimental and/or theoretical studies of peptides from Fasciola hepatica cathepsin proteases or present on 10 Anisakis simplex allergens (Ani s 1 to Ani s 10). In doing so, we combined electrophoresis (1DE), MALDI-TOF Mass Spectroscopy, and MASCOT to seek sequences, Molecular Mechanics + Molecular Dynamics (MM/MD) to generate 3D structures and MISS-Prot to predict PSP scores. MISS-Prot also allows the prediction of PSP proteins in 16 additional species including parasite hosts, fungi pathogens, disease transmission vectors, and biotechnologically relevant organisms.
Subject(s)
Allergens/chemistry , Anisakis/chemistry , Antigens, Helminth/chemistry , Fasciola hepatica/metabolism , Helminth Proteins/chemistry , Online Systems , Peptides/chemistry , Algorithms , Amino Acid Sequence , Animals , Cathepsin L/chemistry , Computational Biology , Computer Simulation , Discriminant Analysis , Fasciola hepatica/chemistry , Humans , Internet , Markov Chains , Models, Molecular , Molecular Sequence Data , Neural Networks, Computer , Protein Structure, Tertiary , ROC Curve , SoftwareABSTRACT
Anisakiosis is a nematodosis with high prevalence in Spain. In this work we (a) investigated whether a recently introduced ELISA of Anisakis simplex-specific IgE in serum suffers from cross-reactivity with other common allergens; (b) used this assay to obtain an estimate of the prevalence of A. simplex-specific IgE in the population of Madrid; and (c) related positivity to fish consumption habits. No evidence of cross-reactivity between the ELISA and other allergens was found. The prevalence of positivity was 12.4% (11.7% among healthy subjects and 16% among patients with non-digestive non-allergic pathologies). All interviewed subjects reported consumption of uncooked fish (known to be the most likely source of infection); in addition, positivity was more prevalent among subjects who habitually consumed fresh and possibly undercooked fish than among those who generally consumed frozen fish or boiled or baked fish. These results are discussed in relation to the much lower prevalence observed in Galicia (N.W. Spain).
