Descemet’s stripping automated endothelial keratoplasty for congenital hereditary endothelial dystrophy

Congenital hereditary endothelial dystrophy (CHED), presents in infancy or early childhood with bilateral clouding of corneas. This condition has previously been managed surgically with penetrating keratoplasty (PKP). Performing PKP in pediatric patients has its own set of difficulties. More recently, there has been growing interest in treating this condition with Descemet’s stripping automated endothelial keratoplasty (DSAEK). The purpose of this study is to report our experience of successfully performing DSAEK in a child with CHED

Aurintricarboxylic Acid Is a Potent Inhibitor of Influenza A and B Virus Neuraminidases

Background: Influenza viruses cause serious infections that can be prevented or treated using vaccines or antiviral agents, respectively. While vaccines are effective, they have a number of limitations, and influenza strains resistant to currently available anti-influenza drugs are increasingly isolated. This necessitates the exploration of novel anti-influenza therapies. Methodology/Principal Findings: We investigated the potential of aurintricarboxylic acid (ATA), a potent inhibitor of nucleic acid processing enzymes, to protect Madin-Darby canine kidney cells from influenza infection. We found, by neutral red assay, that ATA was protective, and by RT-PCR and ELISA, respectively, confirmed that ATA reduced viral replication and release. Furthermore, while pre-treating cells with ATA failed to inhibit viral replication, pre-incubation of virus with ATA effectively reduced viral titers, suggesting that ATA may elicit its inhibitory effects by directly interacting with the virus. Electron microscopy revealed that ATA induced viral aggregation at the cell surface, prompting us to determine if ATA could inhibit neuraminidase. ATA was found to compromise the activities of virus-derived and recombinant neuraminidase. Moreover, an oseltamivir-resistant H1N1 strain with H274Y was also found to be sensitive to ATA. Finally, we observed additive protective value when infected cells were simultaneously treated with ATA and amantadine hydrochloride, an antiinfluenza drug that inhibits M2-ion channels of influenza A virus. Conclusions/Significance: Collectively, these data suggest that ATA is a potent anti-influenza agent by directly inhibiting th

Patterns of Human Respiratory Viruses and Lack of MERS-Coronavirus in Patients with Acute Upper Respiratory Tract Infections in Southwestern Province of Saudi Arabia

We undertook enhanced surveillance of those presenting with respiratory symptoms at five healthcare centers by testing all symptomatic outpatients between November 2013 and January 2014 (winter time). Nasal swabs were collected from 182 patients and screened for MERS-CoV as well as other respiratory viruses using RT-PCR and multiplex microarray. A total of 75 (41.2%) of these patients had positive viral infection. MERS-CoV was not detected in any of the samples. Human rhinovirus (hRV) was the most detected pathogen (40.9%) followed by non-MERS-CoV human coronaviruses (19.3%), influenza (Flu) viruses (15.9%), and human respiratory syncytial virus (hRSV) (13.6%). Viruses differed markedly depending on age in which hRV, Flu A, and hCoV-OC43 were more prevalent in adults and RSV, hCoV-HKU1, and hCoV-NL63 were mostly restricted to children under the age of 15. Moreover, coinfection was not uncommon in this study, in which 17.3% of the infected patients had dual infections due to several combinations of viruses. Dual infections decreased with age and completely disappeared in people older than 45 years. Our study confirms that MERS-CoV is not common in the southwestern region of Saudi Arabia and shows high diversity and prevalence of other common respiratory viruses. This study also highlights the importance and contribution of enhanced surveillance systems for better infection control

Unveiling Integrated Functional Pathways Leading to Enhanced Respiratory Disease Associated With Inactivated Respiratory Syncytial Viral Vaccine

Respiratory syncytial virus (RSV) infection is a severe threat to young children and the elderly. Despite decades of research, no vaccine has been approved. Notably, instead of affording protection, a formalin-inactivated RSV vaccine induced severe respiratory disease including deaths in vaccinated children in a 1960s clinical trial; however, recent studies indicate that other forms of experimental vaccines can also induce pulmonary pathology in pre-clinical studies. These findings suggest that multiple factors/pathways could be involved in the development of enhanced respiratory diseases. Clearly, a better understanding of the mechanisms underlying such adverse reactions is critically important for the development of safe and efficacious vaccines against RSV infection, given the exponential growth of RSV vaccine clinical trials in recent years. By employing an integrated systems biology approach in a pre-clinical cotton rat model, we unraveled a complex network of pulmonary canonical pathways leading to disease development in vaccinated animals upon subsequent RSV infections. Cytokines including IL-1, IL-6 GRO/IL-8, and IL-17 in conjunction with mobilized pulmonary inflammatory cells could play important roles in disease development, which involved a wide range of host responses including exacerbated pulmonary inflammation, oxidative stress, hyperreactivity, and homeostatic imbalance between coagulation and fibrinolysis. Moreover, the observed elevated levels of MyD88 implicate the involvement of this critical signal transduction module as the central node of the inflammatory pathways leading to exacerbated pulmonary pathology. Finally, the immunopathological consequences of inactivated vaccine immunization and subsequent RSV exposure were further substantiated by histological analyses of these key proteins along with inflammatory cytokines, while hypercoagulation was supported by increased pulmonary fibrinogen/fibrin accompanied by reduced levels of plasma D-dimers. Enhanced respiratory disease associated with inactivated RSV vaccine involves a complex network of host responses, resulting in significant pulmonary lesions and clinical manifestations such as tachypnea and airway obstruction. The mechanistic insight into the convergence of different signal pathways and identification of biomarkers could help facilitate the development of safe and effective RSV vaccine and formulation of new targeted interventions

Humoral Immunogenicity and Efficacy of a Single Dose of ChAdOx1 MERS Vaccine Candidate in Dromedary Camels

MERS-CoV seronegative and seropositive camels received a single intramuscular dose of ChAdOx1 MERS, a replication-deficient adenoviral vectored vaccine expressing MERS-CoV spike protein, with further groups receiving control vaccinations. Infectious camels with active naturally acquired MERS-CoV infection, were co-housed with the vaccinated camels at a ratio of 1:2 (infected:vaccinated); nasal discharge and virus titres were monitored for 14 days. Overall, the vaccination reduced virus shedding and nasal discharge (p = 0.0059 and p = 0.0274, respectively). Antibody responses in seropositive camels were enhancedby the vaccine; these camels had a higher average age than seronegative. Older seronegative camels responded more strongly to vaccination than younger animals; and neutralising antibodies were detected in nasal swabs. Further work is required to optimise vaccine regimens for younger seronegative camels

Seroprevalence of SARS-CoV-2 (COVID-19) among Healthcare Workers in Saudi Arabia: Comparing Case and Control Hospitals

Healthcare workers (HCWs) stand at the frontline for fighting coronavirus disease 2019 (COVID-19) pandemic. This puts them at higher risk of acquiring the infection than other individuals in the community. Defining immunity status among health care workers is therefore of interest since it helps to mitigate the exposure risk. This study was conducted between May 20th and 30th, 2020. Eighty-five hospitals across Kingdom of Saudi Arabia were divided into 2 groups: COVID-19 referral hospitals are those to which RT-PCR-confirmed COVID-19 patients were admitted or referred for management (Case-hospitals). COVID-19 nonaffected hospitals where no COVID-19 patients had been admitted or managed and no HCW outbreak (Control hospitals). Next, seroprevalence of severe acute respiratory syndrome coronavirus 2 among HCWs was evaluated; there were 12,621 HCWs from the 85 hospitals. There were 61 case-hospitals with 9379 (74.3%) observations, and 24 control-hospitals with 3242 (25.7%) observations. The overall positivity rate by the immunoassay was 299 (2.36%) with a significant difference between the case-hospital (2.9%) and the control-group (0.8%) (P value <0.001). There was a wide variation in the positivity rate between regions and/or cities in Saudi Arabia, ranging from 0% to 6.31%. Of the serology positive samples, 100 samples were further tested using the SAS2pp neutralization assay; 92 (92%) samples showed neutralization activity. The seropositivity rate in Kingdom of Saudi Arabia is low and varies across different regions with higher positivity in case-hospitals than control-hospitals. The lack of neutralizing antibodies (NAb) in 8% of the tested samples could mean that assay is a more sensitive assay or that neutralization assay has a lower detection limits; or possibly that some samples had cross-reaction to spike protein of other coronaviruses in the assay, but these were not specific to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)