Clinical Features of Acute Chikungunya Virus Infection in Children and Adults during an Outbreak in the Maldives

The chikungunya virus is an arthritogenic arbovirus that has re-emerged in many tropical and subtropical regions, causing explosive outbreaks. This re-emergence is due to a genomic polymorphism that has increased the vector susceptibility of the virus. The majority of those infected with chikungunya virus exhibit symptoms of fever, rash, and debilitating polyarthralgia or arthritis. Symptoms can persist for weeks, and patients can relapse months later. Fatalities are rare, but individuals of extreme age can develop severe infection. Here, we describe the 2019 outbreak, the second-largest since the virus re-emerged in the Maldives after the 2004 Indian Ocean epidemic, in which a total of 1,470 cases were reported to the Health Ministry. Sixty-seven patients presenting at the main referral tertiary care hospital in the Maldives capital with acute undifferentiated illness were recruited following a negative dengue serology. A novel point-of-care antigen kit was used to screen suspected cases, 50 of which were subsequently confirmed using real-time reverse transcription–polymerase chain reaction. We describe the genotype and polymorphism of Maldives chikungunya virus using phylogenetic analysis. All isolates were consistent with the East Central South African genotype of the Indian Ocean lineage, with a specific E1-K211E mutation. In addition, we explored the clinical and laboratory manifestations of acute chikungunya in children and adults, of which severe infection was found in some children, whereas arthritis primarily occurred in adults. Arthritides in adults occurred irrespective of underlying comorbidities and were associated with the degree of viremia.

Evidence of two deeply divergent co-existing mitochondrial genomes in the Tuatara reveals an extremely complex genomic organization

Animal mitochondrial genomic polymorphism occurs as low-level mitochondrial heteroplasmy and deeply divergent co-existing molecules. The latter is rare, known only in bivalvian mollusks. Here we show two deeply divergent co-existing mt-genomes in a vertebrate through genomic sequencing of the Tuatara (Sphenodon punctatus), the sole-representative of an ancient reptilian Order. The two molecules, revealed using a combination of short-read and long-read sequencing technologies, differ by 10.4% nucleotide divergence. A single long-read covers an entire mt-molecule for both strands. Phylogenetic analyses suggest a 7–8 million-year divergence between genomes. Contrary to earlier reports, all 37 genes typical of animal mitochondria, with drastic gene rearrangements, are confirmed for both mt-genomes. Also unique to vertebrates, concerted evolution drives three near-identical putative Control Region non-coding blocks. Evidence of positive selection at sites linked to metabolically important transmembrane regions of encoded proteins suggests these two mt-genomes may confer an adaptive advantage for an unusually cold-tolerant reptile.

GENOMIC AND EPIGENOMIC PREDICTORS FOR VARIOUS CLINICAL PHENOTYPES OF MYASTHENIA GRAVIS

The aim: To evaluate the relationship of certain alleles of HLA class II leukocyte antigens and the profile of antibodies to various subunits of nicotinic acetylcholine receptors (nAChR), the level of Treg lymphocytes and the serum concentration of anti-inflammatory IL-10 for various clinical myasthenia gravis phenotypes. Materials and methods: We examined 217 patients with thymus-independent myasthenia (n = 42) and thymus-dependent myasthenia, among them patients with thymus hyperplasia (n = 108) and thymoma (n = 67). We used the following methods: ELISA, flow cytometry, light and fluorescence microscopy. Results: Certain genomic (polymorphism of leukocyte HLA-DR antigens) and epigenomic (antibodies to α1 and α7 nAChR subunits, expression of Treg lymphocytes and concentration of cytokines) predictors were identified for various myasthenia phenotypes. The presence of HLA haplotypes DR2 and DR7 in some young patients with M with disease progression led to the development of myasthenia gravis with thymoma (MT) at an older age. The presence of α7 nAChR subunit on thymocyte mitochondria was revealed, which is an additional autoimmune target for autoantibodies in patients with myasthenia gravis. An increase in the concentration of cytokines (IL-4, IL-8, IFN-γ) in all patients with myasthenia gravis was revealed. Conclusions: Estimate the features of the formation of various variants of the immune response in thymus-independent and thymus-dependent myasthenia gravis is a necessary condition for targeted immunocorrection or surgery.

Morphofunctional changes in sable organs and tissues in parvovirus enteritis

High resistance of the caged sable to infectious diseases was noted during the long-term practice of fur-bearing animals breeding. But in recent years, local epizootics in sables, manifested by enteritis, have increasingly begun to appear in fur farms. Parvovirus enteritis was established in the laboratory study of pathological material from sick animals by PCR and RHA. The causative agent of this disease is a virus belonging to the Parvoviridae family, the genome of which is represented by single-stranded DNA. The structure of the virion makes all parvoviruses very stable in the external environment. Carnivore parvoviruses penetrate almost all cells of the body, and reproduce only in the most mitotically active tissues, which is the constantly reproducing intestinal epithelium. Parvoviruses are characterized, on the one hand, by a high (up to 98.5%) degree of genome identity and, on the other hand, by pronounced antigenic variability and genomic polymorphism. This indicates the possibility of interspecific transmission and damage to side (random) hosts, which can serve as a reservoir for recombination and selection of strains with new antigenic properties and species tropism. Since 2017, employees of the Research Institute of Fur-Bearing and Rabbit Breeding named after V.A. Afanasyev, monitoring studies are carried out in various animal farms of the Russian Federation, where sable is bred and from pathological material from sables that have died with clinical signs of enteritis, the DNA of parvovirus is often isolated by PCR. Since the totality of the data obtained suggests the danger of the disease for the unique Russian sable with parvovirus enteritis, the study of morphological and functional changes in sables is an urgent task.

Convergent rewiring of the virulence regulatory network promotes adaptation of Ralstonia solanacearum on resistant tomato

The evolutionary and adaptive potential of a pathogen is a key determinant for successful host colonization and proliferation, but remains poorly known for most of the pathogens. Here, we used experimental evolution combined with phenotyping, genomics and transcriptomics to estimate the adaptive potential of the bacterial plant pathogen Ralstonia solanacearum to overcome the quantitative resistance of the tomato cultivar Hawaii 7996. After serial passaging over 300 generations, we observed pathogen adaptation to within-plant environment of the resistant cultivar but no plant resistance breakdown. Genomic sequence analysis of the adapted clones revealed few genetic alterations but we provide evidence that all but one were gain of function mutations. Transcriptomic analyses revealed that even if different adaptive events occurred in independently evolved clones, there is convergence towards a global rewiring of the virulence regulatory network as evidenced by largely overlapping gene expression profiles. A subset of four transcription regulators, including HrpB, the activator of the type 3 secretion system regulon and EfpR, a global regulator of virulence and metabolic functions, emerged as key nodes of this regulatory network that are frequently targeted to redirect the pathogen’s physiology and improve its fitness in adverse conditions. Significant transcriptomic variations were also detected in evolved clones showing no genomic polymorphism, suggesting that epigenetic modifications regulate expression of some of the virulence network components and play a major role in adaptation as well.

Role of Gene Polymorphism in TNF Alpha Expression and Outcome in Surgical Patients

Introduction: An acute phase response to tissue injury leads to release of pro inflammatory and anti inflammatory cytokines. TNF alpha is an early pro inflammatory cytokine that released in SIRS and largely responsible for clinical manifestation of sepsis. The release of TNF alpha is influenced by messenger RNA transcription of TNF alpha gene. In patients with severe sepsis genomic polymorphism with in the TNF locus found to be associated with TNF alpha production and outcome. Objectives: To evaluate genetic polymorphism of TNF alpha gene at c 850 t locus, influence on TNF alpha expression and on outcome. Materials and Methods: A prospective cohort study conducted at our institute between June 2007 to 2009 in 100 cases. Serum TNF alpha levels measured by using ELISA .TNF alpha polymorphism done at c850t locus in 100 patients and were compared with 70 controls who were normal subjects. By using MEDCALC software mean and standard deviations were calculated, continuous variables were compared using t-test. ROC curves were used to determine the predictive capability of the variables. Results: The most common polymorphism observed was CT in 51 patients. The significant different TNF alpha level expression between the three groups were observed. Significant Tallele was observed in cases (100) when compared with controls (70), p= 0.0002. Conclusion: Genetic polymorphism of TNF alpha gene may play critical role in stress response and outcome of the patient but it needs to be validated in large number of population.