Factors affecting development of Clostridium difficile infection in hospitalized pediatric patients in the country Georgia

Abstract Objective Main aims of our study were to investigate occurrence of Clostridium difficile among hospitalized pediatric patients in Georgia and examine risk factors for the development of C. difficile infection. During our study we tested and piloted the real-time PCR diagnostic systems for rapid and simultaneous identification of C. difficile and number of other pathogens in our facility settings. A cross-sectional study has been performed in children less than 18 years of age in two pediatric hospitals in Georgia, between May 2016 and December 2017. Stool specimens negative by the conventional bacteriology analysis were analyzed for the presence of C. difficile and several viral and protozoa pathogens using enzyme immune assay and polymerase chain reaction. In total samples from 220 hospitalized children with gastroenteritis symptoms were analyzed in this study. Results The average age of the study participants was 4.7 years. Overall 23 children were identified positive for C. difficile (10.5%). Antibiotic exposure within 2 months preceding the onset of diarrhea was associated with an increased risk of C. difficile infections. The risk was greatest with cephalosporins, followed by penicillins, carbapenems and macrolides. Clostridium difficile is an important cause of healthcare-associated diarrhea in pediatric population of Georgia

Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans.

Interactions of killer cell immunoglobulin-like receptors (KIRs) with major histocompatibility complex (MHC) class I ligands diversify natural killer cell responses to infection. By analyzing sequence variation in diverse human populations, we show that the KIR3DL1/S1 locus encodes two lineages of polymorphic inhibitory KIR3DL1 allotypes that recognize Bw4 epitopes of protein">HLA-A and HLA-B and one lineage of conserved activating KIR3DS1 allotypes, also implicated in Bw4 recognition. Balancing selection has maintained these three lineages for over 3 million years. Variation was selected at D1 and D2 domain residues that contact HLA class I and at two sites on D0, the domain that enhances the binding of KIR3D to HLA class I. HLA-B variants that gained Bw4 through interallelic microconversion are also products of selection. A worldwide comparison uncovers unusual KIR3DL1/S1 evolution in modern sub-Saharan Africans. Balancing selection is weak and confined to D0, KIR3DS1 is rare and KIR3DL1 allotypes with similar binding sites predominate. Natural killer cells express the dominant KIR3DL1 at a high frequency and with high surface density, providing strong responses to cells perturbed in Bw4 expression

Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes

Natural killer (NK) cells contribute to the essential functions of innate immunity and reproduction. Various genes encode NK cell receptors that recognize the major histocompatibility complex (MHC) Class I molecules expressed by other cells. For primate NK cells, the killer-cell immunoglobulin-like receptors (KIR) are a variable and rapidly evolving family of MHC Class I receptors. Studied here is KIR3DL1/S1, which encodes receptors for highly polymorphic human HLA-A and -B and comprises three ancient allelic lineages that have been preserved by balancing selection throughout human evolution. While the 3DS1 lineage of activating receptors has been conserved, the two 3DL1 lineages of inhibitory receptors were diversified through inter-lineage recombination with each other and with 3DS1. Prominent targets for recombination were D0-domain polymorphisms, which modulate enhancer function, and dimorphism at position 283 in the D2 domain, which influences inhibitory function. In African populations, unequal crossing over between the 3DL1 and 3DL2 genes produced a deleted KIR haplotype in which the telomeric “half” was reduced to a single fusion gene with functional properties distinct from its 3DL1 and 3DL2 parents. Conversely, in Eurasian populations, duplication of the KIR3DL1/S1 locus by unequal crossing over has enabled individuals to carry and express alleles of all three KIR3DL1/S1 lineages. These results demonstrate how meiotic recombination combines with an ancient, preserved diversity to create new KIR phenotypes upon which natural selection acts. A consequence of such recombination is to blur the distinction between alleles and loci in the rapidly evolving human KIR gene family