Impact of Delaying Effective and Cost-Effective Policy Decisions: An Example From Cervical Cancer Prevention in Norway

Introduction. Delayed implementation of evidence-driven interventions has consequences that can be formally evaluated. In Norway, programs to prevent cervical cancer (CC)—screening and treatment of precancerous lesions and prophylactic vaccination against human papillomavirus (HPV) infection—have been implemented, but each encountered delays in policy implementation. To examine the effect of these delays, we project the outcomes that would have been achieved with timely implementation of two policy changes compared with the de facto delays in implementation (in Norway). Methods. We used a multimodeling approach that combined HPV transmission and cervical carcinogenesis to estimate the health outcomes and timeline for CC elimination associated with the implementation of two CC prevention policy decisions: a multicohort vaccination program of women up to age 26 years with bivalent vaccine in 2009 compared with actual “delayed” implementation in 2016, and a switch from cytology to primary HPV-based testing in 2015 compared with “delayed” rollout in 2020. Results. Timely implementation of two policy changes compared with current Norwegian prevention policy timeline could have averted approximately 970 additional cases (range of top 10 sets: 830–1060) and accelerated the CC elimination timeline by around 4 years (from 2039 to 2035). Conclusions. If delaying implementation of effective and cost-effective interventions is being considered, the decision-making process should include quantitative analyses on the effects of delays.

Predictors of severe forms of rotaviral infection in children

Rotavirus infection (RVI) is one of the most common childhood diseases. The study of predictors of severe forms of this disease is of undoubted interest.Aim. Based on the study of the characteristics of the premorbid background, life history and clinical and laboratory parameters, determine predictors of severe forms of RVI.Patients and methods. In the departments of intestinal infections and resuscitation and intensive care of Pediatric Research and Clinical Center for Infectious Diseases in the period 2018 – 202. a retrospective study of 962 children aged 2 months to 2 years with rotavirus infection was carried out. he severity of the condition was assessed using the Clarke scale. To identify the most significant predictors of the development of severe forms of RVI, two groups of patients were compared: severe (> 16 points) and moderate (≤16 points) forms of RVI. Comparison of the frequency of occurrence of signs in the groups was performed using the Pearson χ2 test and Fisher’s exact method. The forecasting model was developed using discriminant analysis of the statistical package Statistica for Windows.Results. Severe forms of RVI were detected in 65 children. Among the patients with severe forms of RVI, there were no patients with completed preventive vaccination. Patients with severe forms of RVI were admitted to the hospital in the late stages of the disease and had a higher score on the CDS scale. Based on the research carried out, a model for predicting severe forms of RVI was developed. The features included in the model were: the day of illness at admission, the patient’s age, prehospital prescription of antibacterial drugs, the absence of completed vaccination against RVI, and the severity of dehydration. Assessment of the quality of the created model showed that the classification ability was 97.7%.Conclusion. Predictors of severe forms of RVI include admission to a hospital in the late stages of the disease with severe dehydration, early age, prehospital antibiotics and forced transfer to artificial feeding, and absence of completed prophylactic vaccination.

A Review of UK-Registered and Candidate Vaccines for Bovine Respiratory Disease

Vaccination is widely regarded as a cornerstone in animal or herd health and infectious disease management. Nineteen vaccines against the major pathogens implicated in bovine respiratory disease are registered for use in the UK by the Veterinary Medicines Directorate (VMD). However, despite annual prophylactic vaccination, bovine respiratory disease is still conservatively estimated to cost the UK economy approximately £80 million per annum. This review examines the vaccine types available, discusses the surrounding literature and scientific rationale of the limitations and assesses the potential of novel vaccine technologies.

Exacerbated AIDS progression by PD-1 blockade during therapeutic vaccination in chronically SIV-infected rhesus macaques after ART treatment interruption

The persistence of latent HIV-1-infected cells, named the latent reservoir, is the major barrier to HIV-1 eradication, and the formation and maintenance of latent reservoir might be exacerbated by activation of the immunoinhibitory pathway and dysfunction of CD8 + T cells during HIV-1 infection. Our previous findings demonstrated that prophylactic vaccination combined with PD-1 blockade generated distinct immune response profiles and conferred effective control of highly pathogenic SIVmac239 infection in rhesus macaques. However, to our surprise, herein we found that a therapeutic vaccination in combination with PD-1 blockade resulted in activation of the viral reservoir, faster viral rebound after treatment interruption, accelerated acquired immune deficiency syndrome (AIDS) progression and ultimately death in chronically SIV-infected macaques after ART treatment interruption. Our study further demonstrated that the SIV provirus was preferentially enriched in PD-1 + CD4 + T cells due to their susceptibility to viral entry, potent proliferation ability and inability to perform viral transcription. In addition, the viral latency was effectively reactivated upon PD-1 blockade. Together, these results suggest that PD-1 blockade may be a double-edged sword for HIV-1 immunotherapy, and they provide important insight for the rational design of immunotherapy strategies toward an HIV-1 cure. Importance As one of the most challenging public health problems, there is no clinically effective cure strategies against HIV-1 infection yet. We have demonstrated that prophylactic vaccination combined with PD-1 blockade generated distinct immune response profiles and conferred better control of highly pathogenic SIVmac239 infection in rhesus macaques. In the present study, to our surprise, PD-1 blockade during therapeutic vaccination accelerated the reactivation of latent reservoir and then AIDS progression in chronically SIV-infected macaques after ART treatment interruption. Our further study demonstrated that the latent SIV provirus was preferentially enriched in PD-1 + CD4 + T cells because of its susceptibility of viral entry, inhibition of SIV transcription and potent ability of proliferation, and the viral latency was effectively reactivated by PD-1 blockade. Therefore, PD-1 blockade might be a double-edged sword for AIDS therapy. These findings provoke extensive interests to further exploit novel therapeutic treatment against HIV-1 infection and other emerging infectious diseases.

Improving Therapeutic Vaccination against Hepatitis B—Insights from Preclinical Models of Immune Therapy against Persistent Hepatitis B Virus Infection

Chronic hepatitis B affects more than 250 million individuals worldwide, putting them at risk of developing liver cirrhosis and liver cancer. While antiviral immune responses are key to eliminating hepatitis B virus (HBV) infections, insufficient antiviral immunity characterized by failure to eliminate HBV-infected hepatocytes is associated with chronic hepatitis B. Prophylactic vaccination against hepatitis B successfully established protective immunity against infection with the hepatitis B virus and has been instrumental in controlling hepatitis B. However, prophylactic vaccination schemes have not been successful in mounting protective immunity to eliminate HBV infections in patients with chronic hepatitis B. Here, we discuss the current knowledge on the development and efficacy of therapeutic vaccination strategies against chronic hepatitis B with particular emphasis on the pathogenetic understanding of dysfunctional anti-viral immunity. We explore the development of additional immune stimulation measures within tissues, in particular activation of immunogenic myeloid cell populations, and their use for combination with therapeutic vaccination strategies to improve the efficacy of therapeutic vaccination against chronic hepatitis B.

Variants in relation to clinical manifestation of rabies in dogs

Rabies is one among the most dangerous diseases reported to have a wider range of incubation period and clinical signs. The disease is manifested as furious or paralytic forms in dogs. The combined effects of virulence and pathogenicity of the virus along with host immune factors are the main variables leading to variation in manifestation of the disease. This paper reports the finding of a study conducted in rabies positive canine cases to correlate the role of pathophysiological factors in clinical manifestation of rabies. A total of 23 rabies positive cases were studied and their anamnesis collected. Male dogs less than 5 years of age constituted major proportion of rabies positive cases. Site of bite was observed as a critical factor in disease manifestation. Anti-rabies prophylactic vaccination had significant effect as none of the vaccinated animals developed furious form of rabies. But paralytic form was found in irregularly vaccinated dogs, probably due to effect of vaccination imparting partial immune response in these animals.

Quantifying malaria acquired during travel and its role in malaria elimination on Bioko Island

Background Malaria elimination is the goal for Bioko Island, Equatorial Guinea. Intensive interventions implemented since 2004 have reduced prevalence, but progress has stalled in recent years. A challenge for elimination has been malaria infections in residents acquired during travel to mainland Equatorial Guinea. The present article quantifies how off-island contributes to remaining malaria prevalence on Bioko Island, and investigates the potential role of a pre-erythrocytic vaccine in making further progress towards elimination. Methods Malaria transmission on Bioko Island was simulated using a model calibrated based on data from the Malaria Indicator Surveys (MIS) from 2015 to 2018, including detailed travel histories and malaria positivity by rapid-diagnostic tests (RDTs), as well as geospatial estimates of malaria prevalence. Mosquito population density was adjusted to fit local transmission, conditional on importation rates under current levels of control and within-island mobility. The simulations were then used to evaluate the impact of two pre-erythrocytic vaccine distribution strategies: mass treat and vaccinate, and prophylactic vaccination for off-island travellers. Lastly, a sensitivity analysis was performed through an ensemble of simulations fit to the Bayesian joint posterior probability distribution of the geospatial prevalence estimates. Results The simulations suggest that in Malabo, an urban city containing 80% of the population, there are some pockets of residual transmission, but a large proportion of infections are acquired off-island by travellers to the mainland. Outside of Malabo, prevalence was mainly attributable to local transmission. The uncertainty in the local transmission vs. importation is lowest within Malabo and highest outside. Using a pre-erythrocytic vaccine to protect travellers would have larger benefits than using the vaccine to protect residents of Bioko Island from local transmission. In simulations, mass treatment and vaccination had short-lived benefits, as malaria prevalence returned to current levels as the vaccine’s efficacy waned. Prophylactic vaccination of travellers resulted in longer-lasting reductions in prevalence. These projections were robust to underlying uncertainty in prevalence estimates. Conclusions The modelled outcomes suggest that the volume of malaria cases imported from the mainland is a partial driver of continued endemic malaria on Bioko Island, and that continued elimination efforts on must account for human travel activity.

Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry. The current intramuscular vaccines elicit systemic immunity but not necessarily high-level mucosal immunity. Here, we tested a single intranasal dose of our candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (AdCOVID) in inbred, outbred, and transgenic mice. A single intranasal vaccination with AdCOVID elicited a strong and focused immune response against RBD through the induction of mucosal IgA in the respiratory tract, serum neutralizing antibodies, and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. A single AdCOVID dose resulted in immunity that was sustained for over six months. Moreover, a single intranasal dose completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge, preventing weight loss and mortality. These data show that AdCOVID promotes concomitant systemic and mucosal immunity and represents a promising vaccine candidate.

A Review of Registered and Candidate Vaccines for Bovine Respiratory Disease in the UK

Vaccination is widely regarded as a cornerstone in animal or herd health and infectious disease management. Nineteen vaccines against the major pathogens implicated in bovine respiratory disease are registered for use in the UK by the Veterinary Medicines Directorate (VMD). However, despite annual prophylactic vaccination, bovine respiratory disease is still conservatively estimated to cost the UK economy approximately £80 million per annum. This review examines the vaccine types available, discusses the surrounding literature and scientific rationale of the limitations and assesses the potential of novel vaccine technologies.

Safety and Impact of Anti-COVID-19 Vaccines in Psoriatic Patients Treated with Biologics: A Real Life Experience

Since all clinical trials conducted during the development of anti-COVID-19 vaccines have adopted among the exclusion criteria the presence of immunodepression or immunomodulating therapy, to date, the effects of vaccination against the new coronavirus 2 in people under such conditions have yet to be clearly defined. The primary objective of the study is to assess the safety of treatment with biotechnological drugs in patients suffering from moderate–severe psoriasis and subjected to the prophylactic vaccination against SARS-Cov-2. Additionally, the secondary objective of the research is to investigate the existence of a possible impact of anti-COVID-19 vaccination on the natural chronic-relapsing course and the severity of the psoriatic disease. The study included 436 patients with moderate–severe psoriasis, both male and female, in treatment with biologics. The data were collected using the direct interview method. A reduction of 74.13% of average Psoriasis Area Severity Index (PASI )compared to baseline (T0) was found in all subjects; this does not differ significantly from the group that underwent vaccination (73.4%). Moreover; at the end of the study, neither mild nor severe adverse events (ADR) were observed among them. In conclusion, biotechnological drugs used in the management of patients with moderate–severe psoriasis demonstrate a high safety profile also in subjects immunized against SARS-Cov-2.