Development and Validation of Indirect Enzyme-Linked Immunosorbent Assays for Detecting Antibodies to SARS-CoV-2 in Cattle,Swine, and Chicken

Multiple domestic and wild animal species are susceptible to SARS-CoV-2 infection. Cattle and swine are susceptible to experimental SARS-CoV-2 infection. The unchecked transmission of SARS-CoV-2 in animal hosts could lead to virus adaptation and the emergence of novel variants. In addition, the spillover and subsequent adaptation of SARS-CoV-2 in livestock could significantly impact food security as well as animal and public health. Therefore, it is essential to monitor livestock species for SARS-CoV-2 spillover. We developed and optimized species-specific indirect ELISAs (iELISAs) to detect anti-SARS-CoV-2 antibodies in cattle, swine, and chickens using the spike protein receptor-binding domain (RBD) antigen. Serum samples collected prior to the COVID-19 pandemic were used to determine the cut-off threshold. RBD hyperimmunized sera from cattle (n = 3), swine (n = 6), and chicken (n = 3) were used as the positive controls. The iELISAs were evaluated compared to a live virus neutralization test using cattle (n = 150), swine (n = 150), and chicken (n = 150) serum samples collected during the COVID-19 pandemic. The iELISAs for cattle, swine, and chicken were found to have 100% sensitivity and specificity. These tools facilitate the surveillance that is necessary to quickly identify spillovers into the three most important agricultural species worldwide.     

In-situ implant containing PCL-curcumin nanoparticles developed using design of experiments

Context: Polymeric delivery system is useful in reducing pharmacokinetic limitations viz., poor absorption and rapid elimination associated with clinical use of curcumin. Design of experiment is a precise and cost effective tool useful in analyzing the effect of independent variables and their interaction on the product attributes.

Objective: To evaluate the effect of process variables involved in preparation of curcumin-loaded polycaprolactone (PCL) nanoparticles (CPN).

Materials and methods: In the present experiment, CPNs were prepared by emulsification solvent evaporation technique. The effect of independent variables on the dependent variable was analyzed using design of experiments. Anticancer activity of CPN was studied using Ehrlich ascites carcinoma (EAC) model. In-situ implant was developed using PLGA as polymer.

Results and discussion: The effect of independent variables was studied in two stages. First, the effect of drug–polymer ratio, homogenization speed and surfactant concentration on size was studied using factorial design. The interaction of homogenization speed with homogenization time on mean particle size of CPN was then evaluated using central composite design. In the second stage, the effect of these variables (under the conditions optimized for producing particles <500?nm) on percentage drug encapsulation was evaluated using factorial design. CPN prepared under optimized conditions were able to control the development of EAC in Swiss albino mice and enhanced their survival time. PLGA based in-situ implant containing CPN prepared under optimized conditions showed sustained drug release.

Conclusion: This implant could be further evaluated for pharmacological activities.     

Improved hepatitis C treatment response in younger patients: findings from the UK HCV National Register cohort study

In a cohort of 272 treatment-naive individuals with chronic hepatitis C infection acquired on a known date who were enrolled in the UK HCV National Register, a progressive improvement in response to treatment was found with the evolution of antiviral therapies from 20% (25/122) for interferon monotherapy to 63% (55/88) for pegylated interferon+ribavirin therapy. Multivariable analysis results showed increasing age to be associated with poorer response to therapy [odds ratio (OR) 0·84, 95% confidence interval (CI) 0·72-0·99, P=0·03] whereas time since infection was not associated with response (OR 0·93, 95% CI 0·44-1·98, P=0·85). Other factors significantly associated with a positive response were non-type 1 genotype (P<0·0001) and combination therapies (P<0·0001). During the first two decades of chronic HCV infection, treatment at a younger age was found to be more influential in achieving a sustained viral response than treating earlier in the course of infection.     

Neuro-invasion of Chandipura virus mediates pathogenesis in experimentally infected mice

Neuro-tropism is a major feature in many viral infections. Chandipura virus produces neurological symptoms in naturally infected young children and experimentally infected suckling mice. This study was undertaken to find out the neuro-invasive behaviour of Chandipura virus in suckling mice. The suckling mice were infected with the virus via footpad injection. Different tissues were collected at 24-h intervals up to 96-h post infection and processed for virus quantification and histological study. Further confirming the virus predilection to nerves tissues, the adult mice were inoculated with the virus via different routes. The suckling mice experimental results revealed a progressive replication of virus in spinal cord and brain. The progressive-virus replication was not observed in the other tissues like kidney, spleen, liver etc. Histo-pathological lesions noticed in the spinal cord and brain tissues suggested the extensive damages in these tissues. In adult mice experiment, the virus replication observed only in the brain of the mice infected via intra-cerebral route. From this study, we conclude that nervous tissues are predilection sites for Chandipura virus replication in suckling and adult mice. In suckling mice, virus might transmit through nervous tissues for dissemination. In contrast, the adult mice the nervous terminal might not pick up the virus through footpad infection. The pathogenesis in mice might be due to the virus replication mediated damage in the central nervous system.     

Increased measles–mumps–rubella (MMR) vaccine uptake in the context of a targeted immunisation campaign during a measles outbreak in a vaccine-reluctant community in England

Background

Following a measles outbreak in a vaccine-rejecting community between April and September 2011 in South-East England, local health agencies implemented a two-pronged measles–mumps–rubella (MMR) immunisation campaign from August to October offered at the local general practice where most cases were registered. The campaign included (a) accelerated vaccination of children earlier than scheduled (1st dose at 6–11 months, or 2nd dose at 18–39 months), (b) catch-up of those aged over 18 months who had had no MMR immunisations or were late for second MMR. We investigated the impact of the outbreak and campaign on the number of MMR doses given.

Materials and methods

In January 2012, we collected information on MMR vaccination for children registered at the practice aged 6 months–16 years on 1 August 2011, through the child health information system. We counted the number of MMR doses administered in 2011 and compared it to 2008–2010 data. We estimated the proportion vaccinated among the children eligible for the accelerated and catch-up campaign.

Results

The local practice administered 257 MMR doses in 2011, a 114% increase on the average for 2008–2010. Among children eligible for earlier MMR vaccination 5/26 (19%) received a first dose, and 34/57 (60%) a second dose. Among children eligible for catch-up, 20/329 (6%) received their first MMR and 39/121 (32%) their second. Of 1538 children, the proportion completely unimmunised for MMR declined by 3 percentage-points after the outbreak.

Discussion

Uptake of MMR vaccination significantly increased during the outbreak following the immunisation campaign. Those amenable to MMR vaccination seem to have benefited from the campaign more than those with no previous vaccinations. Future evaluations should address what made a few parents change their mind and have their children vaccinated for the first time during the outbreak.     

Serological responses to COVID-19 Comirnaty booster vaccine,London, United Kingdom,September to December 2021

Serum samples were collected pre- and post-booster vaccination with Comirnaty in 626 participants (aged ≥ 50 years) who had received two Comirnaty doses < 30 days apart, two Comirnaty doses ≥ 30 days apart or two Vaxzevria doses ≥ 30 days apart. Irrespective of primary vaccine type or schedule, spike antibody GMTs peaked 2–4 weeks after second dose, fell significantly ≤ 38 weeks later and rose above primary immunisation GMTs 2–4 weeks post-booster. Higher post-booster responses were observed with a longer interval between primary immunisation and boosting.     

Comparison of Cardiac Risk Scores among the East Mediterranean and South Asian Population

BackgroundCardiovascular disease (CVD) is a global burden particularly in developing countries necessitates the periodical monitoring for these vulnerable population. This study aimed to compare four tools to measure the CVD risk between the East Mediterranean and South Asian population.MethodsThis retrospective analysis included 139 patients from East Mediterranean (n=90) and South Asians (n=49) ethnicity who were admitted during the one-year period in a multi-specialty tertiary care hospital located in Tabuk, Saudi Arabia. Four different tools currently in use across the world were used to analyses the CVD risk.ResultsAtherosclerotic Cardiovascular Disease (ASCVD) from American College of Cardiology/American Heart Association (ACC/AHA) was found to be significant (P=0.0000) than World Health Organization/International Society of Hypertension (WHO/ISH) and Framingham Risk Score (FRS) European SCORE (Systematic Coronary Risk Evaluation) memo card from European Society of Cardiology risk prediction charts. Meanwhile, FRS looks equally good as it detects 44.89% of South Asian study population with >10% CVD risk while ACC/AHA detects 46.93%.ConclusionThe present study recommends ACC/AHA cardiac risk estimator to identify the CVD risk in East Mediterranean population. However, the South Asian population needed a population-based tool to assess the accurate CVD risk.     

Investigation of a pertussis outbreak and comparison of two acellular booster pertussis vaccines in a junior school in South East England, 2019

In March 2019, a pertussis outbreak occurred in children in a junior school (7–11 years) in England who had been offered pertussis-containing booster vaccine at 40 months of age. In a case–control investigation, we assessed the extent of transmission and any difference in protection afforded to those who had previously received a booster 3- or 5-component acellular pertussis vaccine (aP). We took oral fluid specimens from the students to determine IgG antibodies against pertussis toxin (anti-PT). Parents of students attending the school were sent a questionnaire on pertussis symptoms and vaccination status was retrieved from general practitioner records for all students. Of 381 students, 134 (35.2%) were classified as pertussis cases, 133 by demonstration of significant anti-PT IgG titres and one clinically. There was no significant difference in the risk of pertussis between students receiving 3-component (33.7%) or 5-component (32.3%) aP boosters. However, pertussis infection differed significantly in school year 4, with 22.9%, 50.0%, 23.7% and 38.1% pertussis cases in years 3, 4, 5 and 6, respectively. The proportion of students with incomplete vaccinations recorded was higher than the proportion of those not covered according to the national reported coverage, possibly contributing to sustained transmission within the school.