Emerging and Re-emerging Arboviral Diseases as a Global Health Problem

Newly emerging or re-emerging infections continue to pose significant global public health threats. This chapter provides an overview of the combinations of factors that led to the emergence of arthropod-borne viruses as human and veterinary health threats, in order to understand the risk associated and how this can be mitigated. Considering the history of emergence of some arboviruses, these epidemics have occurred globally as a result of climate and socioeconomic changes that have allowed the spread to new geographical areas of viruses previously confined to specific ecological niches such as West Nile and Chikungunya, or viruses considered under control such as Dengue, Japanese encephalitis, and Yellow fever. Moreover, the greatest risk for humans derives from the ability of these viruses to adopt transmission cycles involving highly anthropophilic mosquito species. Finally, many other arboviruses are largely ignored despite their potential to emerge globally. The recent epidemic spread of Zika virus throughout the Americas is the evidence that arboviruses are likely to continually emerge and re-emerge and that improved scientific technologies and knowledge is essential to deal with future vector-borne epidemics. Research priorities should therefore focus on surveillance systems and vector control tools, as well as on the development of antiviral molecules or candidate vaccine

Comparison of influenza-specific neutralizing antibody titers determined using different assay readouts and hemagglutination inhibition titers:good correlation but poor agreement

Determination of influenza-specific antibody titers is commonly done using the hemagglutination inhibition assay (HAI) and the viral microneutralization assay (MN). Both assays are characterized by high intra- and inter-laboratory variability. The HAI assay offers little opportunity for standardization. For the MN assay, variability might be due to the use of different assay protocols employing different readouts. We therefore aimed at investigating which of the MN assay readout methods currently in use would be the most suitable choice for a standardized MN assay that could serve as a substitute for the HAI assay. For this purpose, human serum samples were tested for the presence of influenza specific neutralizing antibodies against A/California/7/09 H1N1 (49 sera) or A/Hong Kong/4801/2014 (50 sera) using four different infection readout methods for the MN assay (cytopathic effect, hemagglutination, ELISA, RT qPCR) and using the HAI assay. The results were compared by correlation analysis and by determining the level of agreement before and after normalization to a standard serum. Titers as measured by the 4 MN assay readouts showed good correlation, with high Person's r for most comparisons. However, agreement between nominal titers varied with readouts compared and virus strain used. In addition, Pearson's correlation of MN titers with HAI titers was high but agreement of nominal titers was moderate and the average difference between the readings of two assays (bias) was virus strain-dependent. Normalization to a standard serum did not result in better agreement of assay results. Our study demonstrates that different MN readouts result in nominally different antibody titers. Accordingly, the use of a common and standardized MN assay protocol will be crucial to minimize inter-laboratory variability. Based on reproducibility, cost effectiveness and unbiased assessment of results we elected the MN assay with ELISA readout as most suitable for a possible replacement of the HAI assay

Fluid management in the perioperative setting: mind the kidney

Acute kidney injury (AKI) is one of the most frequent complications in critically ill patients and in the perioperative setting. The anatomical structure and the microvasculature of the kidney makes it highly vulnerable to hypoxia. Although fluid therapy is considered crucial in situations where improvement of cardiac output is needed, it can also contribute to AKI development when administered inappropriately. Hemodilution and anemia during cardio-pulmonary bypass have been demonstrated to be risk factors for AKI and they are likely to be a consequence of fluid administration. In order to assess the perfusion of the kidneys it is necessary to investigate the determinants of delivery of oxygen at the microcirculatory level. Indeed, fluids can decrease the capillary hematocrit and the functional capillary density, affecting the renal oxygenation and increasing the risk of AKI. Monitoring sublingual microcirculation can be a reliable tool to guide fluid administration, aiming to prevent or improve perioperative AKI

Epidemiology of herpes simplex virus type 1 and 2 in Italy: a seroprevalence study over 15 years

Introduction: Herpes simplex viruses (HSV) are among the most widespread causative agents of human viral infections. HSV-2 is one of the commonest causes of genital disease, while HSV-1 is associated primarily with orolabial ulceration; however, recent changes in HSV epidemiology showed an increase in genital and neonatal herpes particularly caused by HSV-1. The main purpose of this study was to assess the seroprevalence of HSV-1 and HSV-2 in a random population in Siena (central Italy) in 2000, 2005 and 2013-2014 and in Bari (southern Italy) in 2005. Moreover, a preliminary study was conducted to investigate the spread of HSV infection in a population of pregnant women and infants in Bari in 2003, 2004 and 2005. Methods: Human serum samples were tested for the presence of specific anti-HSV-1 and anti-HSV-2 IgG antibodies using a commercially available ELISA test. Results and conclusions: For the primary purpose, seroprevalence rates observed in Siena were compared over the years sampled and with the seroprevalence rate found in Bari. Results of seroprevalence in Siena show a decreased trend for both viruses, especially in adolescents and young adults; moreover, HSV-2 seroprevalence rates found in the two cities suggest geographical differences. For the secondary purpose, prevalence rates among pregnant women were compared with the seroprevalence found in women of the general population. No significant difference in prevalence rates were found among pregnant women, while results indicate both viruses are a source of infection in infants

immunogenicity and safety of quadrivalent versus trivalent inactivated subunit influenza vaccine in children and adolescents a phase iii randomized study

Abstract Objectives To analyze the immunogenicity and safety of inactivated subunit quadrivalent influenza vaccine (QIV) versus trivalent influenza vaccine (TIV) in children and adolescents 3–17 years of age. Methods In this phase III, multicenter, double-blind study, 1200 subjects were randomized to receive QIV (n = 402), or TIV with the B-strain of the Victoria lineage (n = 404) or Yamagata lineage (n = 394). The primary objective was to demonstrate non-inferiority of QIV to TIV for immunogenicity against shared influenza strains, based on post-vaccination hemagglutinin inhibition (HI) titers. Secondary objectives were to show superiority of QIV to TIV for immunogenicity against alternate-lineage B-strains, and to further characterize immune response by analyzing virus neutralization and neuraminidase inhibition titers. Reactogenicity and safety were also compared post-vaccination. Results QIV elicited a non-inferior response for shared strains (upper limits of the 95% confidence intervals for the HI geometric mean ratios [GMRs] of TIV/QIV  Conclusions QIV had comparable immunogenicity to TIV for shared strains and superior immunogenicity to the alternate-lineage B-strains in TIV. Safety and tolerability profiles were comparable

Preclinical and Clinical Development of Plant-Made Virus-Like Particle Vaccine against Avian H5N1 Influenza

The recent swine H1N1 influenza outbreak demonstrated that egg-based vaccine manufacturing has an Achille's heel: its inability to provide a large number of doses quickly. Using a novel manufacturing platform based on transient expression of influenza surface glycoproteins in Nicotiana benthamiana, we have recently demonstrated that a candidate Virus-Like Particle (VLP) vaccine can be generated within 3 weeks of release of sequence information. Herein we report that alum-adjuvanted plant-made VLPs containing the hemagglutinin (HA) protein of H5N1 influenza (A/Indonesia/5/05) can induce cross-reactive antibodies in ferrets. Even low doses of this vaccine prevented pathology and reduced viral loads following heterotypic lethal challenge. We further report on safety and immunogenicity from a Phase I clinical study of the plant-made H5 VLP vaccine in healthy adults 18-60 years of age who received 2 doses 21 days apart of 5, 10 or 20 µg of alum-adjuvanted H5 VLP vaccine or placebo (alum). The vaccine was well tolerated at all doses. Adverse events (AE) were mild-to-moderate and self-limited. Pain at the injection site was the most frequent AE, reported in 70% of vaccinated subjects versus 50% of the placebo recipients. No allergic reactions were reported and the plant-made vaccine did not significantly increase the level of naturally occurring serum antibodies to plant-specific sugar moieties. The immunogenicity of the H5 VLP vaccine was evaluated by Hemagglutination-Inhibition (HI), Single Radial Hemolysis (SRH) and MicroNeutralisation (MN). Results from these three assays were highly correlated and showed similar trends across doses. There was a clear dose-response in all measures of immunogenicity and almost 96% of those in the higher dose groups (2 × 10 or 20 µg) mounted detectable MN responses. Evidence of striking cross-protection in ferrets combined with a good safety profile and promising immunogenicity in humans suggest that plant-based VLP vaccines should be further evaluated for use in pre-pandemic or pandemic situations.ClinicalTrials.gov NCT00984945

Emerging influenza strains in the last two decades: A threat of a new pandemic?

In the last 20 years, novel non-seasonal influenza viruses have emerged, most of which have originated from birds. Despite their apparent inability to cause pandemics, with the exception of H1N1 swine influenza virus, these viruses still constitute a constant threat to public health. While general concern has decreased after the peak of the H5N1 virus, in recent years several novel reassorted influenza viruses (e.g., H7N9, H9N2, H10N8) have jumped the host-species barrier and are under surveillance by the scientific community and public health systems. It is still unclear whether these viruses can actually cause pandemics or just isolated episodes. The purpose of this review is to provide an overview of old and novel potential pandemic strains of recent decades

Characterisation of SARS-CoV-2 Lentiviral Pseudotypes and Correlation between Pseudotype-Based Neutralisation Assays and Live Virus-Based Micro Neutralisation Assays

The recent outbreak of a novel Coronavirus (SARS-CoV-2) and its rapid spread across the continents has generated an urgent need for assays to detect the neutralising activity of human sera or human monoclonal antibodies against SARS-CoV-2 spike protein and to evaluate the serological immunity in humans. Since the accessibility of live virus microneutralisation (MN) assays with SARS-CoV-2 is limited and requires enhanced bio-containment, the approach based on "pseudotyping" can be considered a useful complement to other serological assays. After fully characterising lentiviral pseudotypes bearing the SARS-CoV-2 spike protein, we employed them in pseudotype-based neutralisation assays in order to profile the neutralising activity of human serum samples from an Italian sero-epidemiological study. The results obtained with pseudotype-based neutralisation assays mirrored those obtained when the same panel of sera was tested against the wild type virus, showing an evident convergence of the pseudotype-based neutralisation and MN results. The overall results lead to the conclusion that the pseudotype-based neutralisation assay is a valid alternative to using the wild-type strain, and although this system needs to be optimised and standardised, it can not only complement the classical serological methods, but also allows serological assessments to be made when other methods cannot be employed, especially in a human pandemic context