The Re-Emergence of Hepatitis E Virus in Europe and Vaccine Development.

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water or food) or by contact with infected animals and their raw meat products. Some animals, such as pigs, wild boars, sheep, goats, rabbits, camels, rats, etc., are natural reservoirs of HEV, which places people in close contact with them at increased risk of HEV disease. Although hepatitis E is a self-limiting infection, it could also lead to severe illness, particularly among pregnant women, or chronic infection in immunocompromised people. A growing number of studies point out that HEV can be classified as a re-emerging virus in developed countries. Preventative efforts are needed to reduce the incidence of acute and chronic hepatitis E in non-endemic and endemic countries. There is a recombinant HEV vaccine, but it is approved for use and commercially available only in China and Pakistan. However, further studies are needed to demonstrate the necessity of applying a preventive vaccine and to create conditions for reducing the spread of HEV. This review emphasizes the hepatitis E virus and its importance for public health in Europe, the methods of virus transmission and treatment, and summarizes the latest studies on HEV vaccine development.

Age and Gender Trends in the Prevalence of Markers for Hepatitis E Virus Exposure in the Heterogeneous Bulgarian Population.

The prevalence of hepatitis E virus (HEV) in the Bulgarian population remains underestimated. The aim of the present study was to evaluate age and gender trends in HEV prevalence in the heterogeneous Bulgarian population. Stored serum samples from blood donors and different patient sub-populations-kidney recipients (KR), patients with Guillain-Barre syndrome (GBS), Lyme disease (LD), patients with liver involvement and a clinical diagnosis other than viral hepatitis A and E (non-AE), hemodialysis (HD) and HIV-positive patients (HIV)-were retrospectively investigated for markers of past and recent/ongoing HEV infection. The estimated overall seroprevalence of past infection was 10.6%, ranging from 5.9% to 24.5% for the sub-populations evaluated, while the seroprevalence of recent/ongoing HEV infection was 7.5%, ranging from 2.1% to 20.4%. The analysis of the individual sub-populations showed a different prevalence with respect to sex. In regard to age, the cohort effect was preserved, as a multimodal pattern was observed only for the GBS sub-population. Molecular analysis revealed HEV 3f and 3e. The type of the population is one of the main factors on which the anti-HEV prevalence depends, highlighting the need for the development of guidelines related to the detection and diagnosis of HEV infection with regard to specific patient populations.

Severe thrombocytopenia in primary EBV- Infection with no signs of infectious mononucleosis. A case report.

Epstein-Barr virus is a widely spread Herpesvirus. Primary EBV infection affects children and young people, inducing haematological changes, with lymphocytosis being the most common. Moderate symptomless thrombocytopenia is found in 50% of the patients, however, severe thrombocytopenia is exceptionally rare. We present a case report of a 20-year-old man with an acute EBV infection, severe thrombocytopenia, and no signs of infectious mononucleosis.

Hypotheses and facts for genetic factors related to severe COVID-19.

Genome-wide association analysis allows the identification of potential candidate genes involved in the development of severe coronavirus disease 2019 (COVID-19). Hence, it seems that genetics matters here, as well. Nevertheless, the virus's nature, including its RNA structure, determines the rate of mutations leading to new viral strains with all epidemiological and clinical consequences. Given these observations, we herein comment on the current hypotheses about the possible role of the genes in association with COVID-19 severity. We discuss some of the major candidate genes that have been identified as potential genetic factors associated with the COVID-19 severity and infection susceptibility: HLA, ABO, ACE2, TLR7, ApoE, TYK2, OAS, DPP9, IFNAR2, CCR2, etc. Further study of genes and genetic variants will be of great benefit for the prevention and assessment of the individual risk and disease severity in different populations. These scientific data will serve as a basis for the development of clinically applicable diagnostic and prognostic tests for patients at high risk of COVID-19.

Vector-borne and zoonotic infections and their relationships with regional and socioeconomic statuses: An ID-IRI survey in 24 countries of Europe, Africa and Asia.

BACKGROUND: In this cross-sectional, international study, we aimed to analyze vector-borne and zoonotic infections (VBZI), which are significant global threats. METHOD: VBZIs' data between May 20-28, 2018 was collected. The 24 Participatingcountries were classified as lower-middle, upper-middle, and high-income. RESULTS: 382 patients were included. 175(45.8%) were hospitalized, most commonly in Croatia, Egypt, and Romania(P = 0.001). There was a significant difference between distributions of VBZIs according to geographical regions(P < 0.001). Amebiasis, Ancylostomiasis, Blastocystosis, Cryptosporidiosis, Giardiasis, Toxoplasmosis were significantly more common in the Middle-East while Bartonellosis, Borreliosis, Cat Scratch Disease, Hantavirus syndrome, Rickettsiosis, Campylobacteriosis, Salmonellosis in Central/East/South-East Europe; Brucellosis and Echinococcosis in Central/West Asia; Campylobacteriosis, Chikungunya, Tick-borne encephalitis, Visceral Leishmaniasis, Salmonellosis, Toxoplasmosis in the North-Mediterranean; CCHF, Cutaneous Leishmaniasis, Dengue, Malaria, Taeniasis, Salmonellosis in Indian Subcontinent; Lassa Fever in West Africa. There were significant regional differences for viral hemorrhagic fevers(P < 0.001) and tick-borne infections(P < 0.001), and according to economic status for VBZIs(P < 0.001). The prevalences of VBZIs were significantly higher in lower-middle income countries(P = 0.001). The most similar regions were the Indian Subcontinent and the Middle-East, the Indian Subcontinent and the North-Mediterranean, and the Middle-East and North-Mediterranean regions. CONCLUSIONS: Regional and socioeconomic heterogeneity still exists for VBZIs. Control and eradication of VBZIs require evidence-based surveillance data, and multidisciplinary efforts.

West Nile Fever - Clinical and Epidemiological Characteristics. Review of the Literature and Contribution with Three Clinical Cases.

West Nile fever (WNF) is a vector-borne infection caused by a Flavivirus-West Nile virus (WNV). WNV is transmitted by mosquitoes, and birds are the major natural reservoir. A recent increase in the number of the WNF cases has been reported in Europe, the Balkans, and Bulgaria. We herein present the clinical course, laboratory and imaging findings of three patients - a female and two male patients, who were diagnosed with WNF. They were investigated in an epidemiological study, and by using clinical observation, laboratory and microbiological methods, serological tests for specific anti-WNV antibodies detection, molecular biology techniques (polymerase chain reaction, PCR), computed tomography (CT) and magnetic resonance imaging (MRI). The patients presented with fever, headache, drowsiness, and dizziness and anti-WNV antibodies were detected in their serum samples. WNV-RNA was found in a blood sample from the female patient. Both anti-WNV IgM and Herpes simplex virus-1 DNA were detected in a cerebrospinal fluid sample from one of the men. The three patients recovered from the disease after a long convalescent period. WNF has no specific signs, laboratory and imaging findings and could be a life-threatening condition, leading to serious complications. Therefore, WNF should be taken into consideration during the summer when the vector of the infection is active.

Immunological aspects of COVID-19: What do we know?

The newly emerged coronavirus (severe acute respiratory syndrome coronavirus 2 SARS-CoV-2) and the disease that it causes coronavirus disease 2019 (COVID-19) have changed the world we know. Yet, the origin and evolution of SARS-CoV-2 remain mostly vague. Many virulence factors and immune mechanisms contribute to the deteriorating effects on the organism during SARS-CoV-2 infection. Both humoral and cellular immune responses are involved in the pathophysiology of the disease, where the principal and effective immune response towards viral infection is the cell-mediated immunity. The clinical picture of COVID-19, which includes immune memory and reinfection, remains unclear and unpredictable. However, many hopes are put in developing an effective vaccine against the virus, and different therapeutic options have been implemented to find effective, even though not specific, treatment to the disease. We can assume that the interaction between the SARS-CoV-2 virus and the individual's immune system determines the onset and development of the disease significantly.

Equilibrium statistics of an inelastically bouncing ball, subject to gravity and a random force.

We consider a particle moving on the half line x > 0 and subject to a constant force in the -x direction plus a delta-correlated random force. At x = 0 the particle is reflected inelastically. The velocities just after and before the reflection satisfy v(f) = -r v(i), where r is the coefficient of restitution. This simple model is of interest in connection with studies of driven granular matter in a gravitational field. With an exact analytical approach and simulations we study the steady-state distribution function P(x,v).

Randomly accelerated particle in a box: mean absorption time for partially absorbing and inelastic boundaries.

Consider a particle which is randomly accelerated by Gaussian white noise on the line segment 0

Equilibrium of a confined, randomly accelerated, inelastic particle: is there inelastic collapse?

We consider the one-dimensional motion of a particle randomly accelerated by Gaussian white noise on the line segment 00 of the velocity just after reflection from the boundary vanish.

Effect of interactions on molecular fluxes and fluctuations in the transport across membrane channels.

Transport of molecules across membrane channels is investigated theoretically using exactly solvable one-dimensional discrete-state stochastic models. An interaction between molecules and membrane pores is modeled via a set of binding sites with different energies. It is shown that the interaction potential strongly influences the particle currents as well as fluctuations in the number of translocated molecules. For small concentration gradients, the attractive sites lead to largest currents and fluctuations, while the repulsive interactions yield the largest fluxes and dispersions for large concentration gradients. Interaction energies that lead to maximal currents and maximal fluctuations are the same only for locally symmetric potentials, where transition states are equally distant from the neighboring binding sites, while they differ for the locally asymmetric potentials. The conditions for the most optimal translocation transport with maximal current and minimal dispersion are discussed. It is argued that, in this case, the interaction strength is independent of local symmetry of the potential of mean forces. In addition, the effect of the global asymmetry of the interaction potential is investigated, and it is shown that it also strongly affects the particle translocation dynamics. These phenomena can be explained by analyzing the details of the particle entering and leaving the binding sites in the channel.

Translocation of polymers with folded configurations across nanopores.

The transport of polymers with folded configurations across membrane pores is investigated theoretically by analyzing simple discrete stochastic models. The translocation dynamics is viewed as a sequence of two events: motion of the folded segment through the channel followed by the linear part of the polymer. The transition rates vary for the folded and linear segments because of different interactions between the polymer molecule and the pore. It is shown that the translocation time depends nonmonotonously on the length of the folded segment for short polymers and weak external fields, while it becomes monotonous for long molecules and large fields. Also, there is a critical interaction between the polymers and the pore that separates two dynamic regimes. For stronger interactions, the folded polymer moves slower, while for weaker interactions, the linear chain translocation is the fastest. In addition, our calculations show that the folding does not change the translocation scaling properties of the polymer. These phenomena can be explained by the interplay between translocation distances and transition rates for the folded and linear segments of the polymer. Our theoretical results are applied for analysis of experimental translocations through solid-state nanopores.

Effect of orientation in translocation of polymers through nanopores.

The motion of polymers with inhomogeneous structure through nanopores is discussed theoretically. Specifically, we consider the translocation dynamics of polymers consisting of double-stranded and single-stranded blocks. Since only the single-stranded chain can go through the nanopore the double-stranded segment has to unzip before the translocation. Utilizing a simple analytical model, translocation times are calculated explicitly for different polymer orientations, i.e., when the single-stranded block enters the pore first and when the double-stranded segment is a leading one. The dependence of the translocation dynamics on external fields, energy of interaction in the double-stranded segment, size of the polymer, and the fraction of double-stranded monomers is analyzed. It is found that the order of entrance into the pore has a significant effect on the translocation dynamics. The theoretical results are discussed using free-energy landscape arguments.