Genotype Distribution and Characteristics of Chronic Hepatitis C Infection in Estonia, Latvia, Lithuania, and Ukraine: The RESPOND-C Study.

Background and objectives: Since 2013, highly effective direct-acting antiviral (DAA) treatment for chronic hepatitis C (CHC) has become available, with cure rates exceeding 95%. For the choice of optimal CHC treatment, an assessment of the hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage is necessary. Information about the distribution of these parameters among CHC patients in Estonia, Latvia, and Lithuania (the Baltic states) and especially in Ukraine is scarce. This study was performed to obtain epidemiologic data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (the Baltic states) and lower-middle-income (Ukraine) countries. Materials and methods: The retrospective RESPOND-C study included 1451 CHC patients. Demographic and disease information was collected from medical charts for each patient. Results: The most common suspected mode of viral transmission was blood transfusions (17.8%), followed by intravenous substance use (15.7%); however, in 50.9% of patients, the exact mode of transmission was not clarified. In Ukraine (18.4%) and Estonia (26%), transmission by intravenous substance use was higher than in Lithuania (5%) and Latvia (5.3%). Distribution of HCV GT among patients with CHC was as follows: GT1-66.4%; GT3-28.1; and GT2-4.1%. The prevalence of GT1 was the highest in Latvia (84%) and the lowest in Ukraine (63%, p < 0.001). Liver fibrosis stages were distributed as follows: F0-12.2%, F1-26.3%, F2-23.5%, F3-17.1%, and F4-20.9%. Cirrhosis (F4) was more prevalent in Lithuanian patients (30.1%) than in Estonians (8.1%, p < 0.001). Conclusions: This study contributes to the knowledge of epidemiologic characteristics of HCV infection in the Baltic states and Ukraine. The data regarding the patterns of HCV GT and fibrosis stage distribution will be helpful for the development of national strategies to control HCV infection in the era of DAA therapy.

Experimental validation of genetic selection for resistance against Streptococcus agalactiae via different routes of infection in the commercial Nile tilapia breeding programme.

The objective of this study was to validate the genetic selection for resistance to streptococcosis under experimental challenge conditions in a commercial population of Nile tilapia. Further, effects of using two different routes of infection of Streptococcus agalactiae; intraperitoneal injection (IP) and cohabitation with the shedder fish (cohab), on the genomic parameters, prediction accuracy and response to selection are compared. The comparison was made between two different lines of fish; one selected for S. agalactiae resistance for one generation and randomly mated for two generations (to mimic the multiplication activities occurring in distribution channels and hatcheries); and the other unselected. 1,500 fish, each from these two lines, were used for the experimental challenge test. Survival analysis using Kaplan-Meier estimators and Hazard's ratio was used to quantify differences in mortality between the two lines. Further genomic analysis was performed with 2,684 fish and 35,745 SNPs using both univariate and bivariate GBLUP models. Genetic selection for resistance to S. agalactiae led to the significant (p < .001) reduction in the risk of death by 65% in the selected line, compared to the unselected line. Similarly, the risk of death via cohabitation route of infection significantly (p < .01) decreased by 80%, compared to IP. The genetic correlation between these two routes of infection was ~0.9. Genetic selection changed the impact of the routes of infection, with the change in the distribution of estimated breeding values and the gain of 3.04 ± 1.25 days as selection response (p < .05).

Macrophages: Key Cellular Players in HIV Infection and Pathogenesis.

Although cells of the myeloid lineages, including tissue macrophages and conventional dendritic cells, were rapidly recognized, in addition to CD4+ T lymphocytes, as target cells of HIV-1, their specific roles in the pathophysiology of infection were initially largely neglected. However, numerous studies performed over the past decade, both in vitro in cell culture systems and in vivo in monkey and humanized mouse animal models, led to growing evidence that macrophages play important direct and indirect roles as HIV-1 target cells and in pathogenesis. It has been recently proposed that macrophages are likely involved in all stages of HIV-1 pathogenesis, including virus transmission and dissemination, but above all, in viral persistence through the establishment, together with latently infected CD4+ T cells, of virus reservoirs in many host tissues, the major obstacle to virus eradication in people living with HIV. Infected macrophages are indeed found, very often as multinucleated giant cells expressing viral antigens, in almost all lymphoid and non-lymphoid tissues of HIV-1-infected patients, where they can probably persist for long period of time. In addition, macrophages also likely participate, directly as HIV-1 targets or indirectly as key regulators of innate immunity and inflammation, in the chronic inflammation and associated clinical disorders observed in people living with HIV, even in patients receiving effective antiretroviral therapy. The main objective of this review is therefore to summarize the recent findings, and also to revisit older data, regarding the critical functions of tissue macrophages in the pathophysiology of HIV-1 infection, both as major HIV-1-infected target cells likely found in almost all tissues, as well as regulators of innate immunity and inflammation during the different stages of HIV-1 pathogenesis.

An alternative to airborne droplet transmission route of SARS-CoV-2, the feco-oral route, as a factor shaping COVID-19 pandemic.

The Chinese scenario, a rapid increase in the frequency of SARS-CoV-2 infections and sudden decline, is uncommon worldwide. Enormous differences in COVID-19 severity among individual countries are the striking findings of the pandemics. It has been demonstrated that a mild course of COVID-19 is associated with gastrointestinal symptoms, less inflammatory response, and better prognosis. The presence of SARS-CoV-2 was observed longer in the gastrointestinal tract than in respiratory swabs, promoting feco-oral transmissions and mild virus attenuation. The spread of the pandemic and its severity might, consequently, depends on the dominant environmental route of infection and emerging immunity. We hypothesize that the feco-oral SARS-CoV-2 transmission may help to achieve the long-term immunity against COVID-19, since it enables the continuous contact with viral antigens in the gastrointestinal tract, resulting in lower mortality rate. To conclude, countries producing rice through traditional methods developed rapidly emerging long-lasting population immunity, possibly through increased SARS-CoV-2 antigen exposure in the gastrointestinal tract. Our hypothesis brings attention to this potential route of herd immunity against SARS-CoV-2 which warrants further investigation in the future.

Evaluation of the clinical evolution and transmission of SARS-CoV-2 infection in cats by simulating natural routes of infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current pandemic disease denominated as Coronavirus Disease 2019 (COVID-19). Several studies suggest that the original source of this virus was a spillover from an animal reservoir and its subsequent adaptation to humans. Of all the different animals affected, cats are one of the most susceptible species. Moreover, several cases of natural infection in domestic and stray cats have been reported in the last few months. Although experimental infection assays have demonstrated that cats are successfully infected and can transmit the virus to other cats by aerosol, the conditions used for these experiments have not been specified in terms of ventilation. We have, therefore, evaluated the susceptibility of cats using routes of infection similar to those expected under natural conditions (exposure to a sneeze, cough, or contaminated environment) by aerosol and oral infection. We have also evaluated the transmission capacity among infected and naïve cats using different air exchange levels. Despite being infected using natural routes and shed virus for a long period, the cats did not transmit the virus to contact cats when air renovation features were employed. The infected animals also developed gross and histological lesions in several organs. These outcomes confirm that cats are at risk of infection when exposed to infected people, but do not transmit the virus to other cats with high rates of air renovation.

Global stability of an age-structured infection model in vivo with two compartments and two routes.

In this paper, for an infection age model with two routes, virus-to-cell and cell-to-cell, and with two compartments, we show that the basic reproduction ratio $ R_0 $ gives the threshold of the stability. If $ R_0 > 1 $, the interior equilibrium is unique and globally stable, and if $ R_0 \le 1 $, the disease free equilibrium is globally stable. Some stability results are obtained in previous research, but, for example, a complete proof of the global stability of the disease equilibrium was not shown. We give the proof for all the cases, and show that we can use a type reproduction number for this model.

Differential Immune Response Following Intranasal and Intradermal Infection with Francisella tularensis: Implications for Vaccine Development.

Francisella tularensis (Ft) is a Gram-negative, facultative intracellular coccobacillus that is the etiological agent of tularemia. Interestingly, the disease tularemia has variable clinical presentations that are dependent upon the route of infection with Ft. Two of the most likely routes of Ft infection include intranasal and intradermal, which result in pneumonic and ulceroglandular tularemia, respectively. While there are several differences between these two forms of tularemia, the most notable disparity is between mortality rates: the mortality rate following pneumonic tularemia is over ten times that of the ulceroglandular disease. Understanding the differences between intradermal and intranasal Ft infections is important not only for clinical diagnoses and treatment but also for the development of a safe and effective vaccine. However, the immune correlates of protection against Ft, especially within the context of infection by disparate routes, are not yet fully understood. Recent advances in different animal models have revealed new insights in the complex interplay of innate and adaptive immune responses, indicating dissimilar patterns in both responses following infection with Ft via different routes. Further investigation of these differences will be crucial to predicting disease outcomes and inducing protective immunity via vaccination or natural infection.

Development of an in vivo model for Toxoplasma gondii infections in chickens and turkeys simulating natural routes of infection.

Turkeys and chickens were orally infected with tissue cysts (one mouse brain) or oocysts (103, 105 or 106 oocysts) of three T. gondii strains of the clonal types II and III (ME49, CZ-Tiger, NED) to investigate the influence of the applied T. gondii strain and infective doses on the distribution of T. gondii in several organs and tissues and the serologic response of chickens and turkeys. Organ samples from 16 different tissues, including heart, brain, muscles and gizzard were analyzed by PCR. Brain and heart were found most frequently positive for T. gondii DNA in both species, followed by gizzard. Serological analysis with kinetic ELISA for turkey samples and IFAT for chicken samples were performed once a week. In both species a dose-depending serological response was found. Turkeys seroconverted one week after infection with CZ-Tiger strain and medium and high doses of ME49 oocysts. In chickens, infection with medium and high doses of CZ-Tiger led to seroconversion one week p.i. Frequency of T. gondii positive organs showed a trend of a dose-effect in both species after infection with the type II strains. The NED strain showed low virulence in chickens and turkeys, demonstrated by clearly less T. gondii positive organs. Infection with tissue cysts of all three strains revealed T. gondii stages in tissues of turkeys and chickens. In conclusion, our data show a risk for human infection with T. gondii due to consumption of chicken and turkey meat.

Transmission, diagnosis, and management of hepatitis E: an update.

Hepatitis E virus (HEV) infection is an important public health concern in many developing countries, causing waterborne outbreaks as well as sporadic autochthonous hepatitis. HEV is mainly transmitted by the fecal-oral route in endemic areas through drinking of contaminated water. However, zoonotic transmission from animal reservoirs to humans has also been suggested. Three additional routes of HEV transmission have been proposed to occur: blood borne, human to human, and vertical transmission from mother to child. Acute HEV infection is usually diagnosed by detecting specific anti-HEV antibodies. However, the performance of the available assays in different settings is not optimal. Analysis of HEV ribonucleic acid in biologic specimens such as stools, serum, and liver biopsy by using nucleic acid amplification techniques is also employed. Nonetheless, additional consensus regarding the best technologies suitable for serosurveys and diagnosis of acute HEV infection is also needed. This review article summarizes the current status of HEV infection end epidemiology with particular emphasis in transmission, diagnosis, and clinical management.