MSD (Netherlands)

Psychotic symptoms are a prevalent yet underrecognized feature of borderline personality disorder (BPD), with studies estimating their occurrence in up to 60% of patients. Despite their clinical and theoretical relevance, these phenomena are marginalized in contemporary diagnostic frameworks, which emphasize affective instability and interpersonal dysfunction while minimizing impairments in reality testing. We review the historical roots of BPD as a schizophrenia-like condition and examine the phenomenology of hallucinations and delusions in this population. Drawing on psychoanalytic object-relations theory, particularly the contributions of Otto Kernberg and John Gunderson, we propose that psychotic symptoms in BPD serve an object-restitutive function, preserving internal relational continuity amid psychic disintegration. We argue that these symptoms are neither incidental nor epiphenomenal but reflect core features of the disorder that warrant greater attention in diagnosis and treatment. Improved clinical recognition and theoretically informed interventions are essential to addressing this neglected dimension of BPD.

Background/Objectives: To this day, rabies remains a significant global threat. This threat remains even with the availability of vaccines for humans, wildlife, and domestic animals, which are used as part of a series of interventions to attempt to control the infection and disease. The number of annual human deaths from rabies globally remains significant, with infections being mainly caused by domestic dogs. Although a number of vaccines exist for domestic animals, most contain inactivated rabies virus with adjuvants. Methods: To investigate alternatives to conventional rabies vaccines for dogs and cats, we developed a novel, non-adjuvanted, low-volume (0.5 mL) vaccine, based on the Venezuelan equine encephalitis virus (VEEV) TC-83-derived RNA particle (RP) expressing the rabies glycoprotein (G). This novel vaccine combines the safety profile of a non-adjuvanted vaccine while inducing consistently high efficacy and an extended duration of immunity similar to that shown by adjuvanted vaccines. Results: In multiple studies, we demonstrated that young kittens and puppies can be safely vaccinated without serious adverse effects. In graded dose experiments with cats and dogs, the RNA particle vaccine induced neutralizing levels of antibodies. Additionally, in vaccination/challenge studies, 100% protection from virulent rabies was demonstrated in excess of three years post-vaccination from a single dose at 12 weeks of age in both dogs and cats. The safety of the RP-Rabies vaccine in dogs and cats as young as twelve weeks of age was demonstrated in field safety studies using two vaccine serials formulated at a field dose. Conclusions: Data from these studies suggest that the RP-Rabies vaccine offers an excellent alternative to current vaccines combining the safety of a non-adjuvanted vaccine in a low-volume, single dose with the induction of an extended duration of immunity of at least three years in both dogs and cats.

IntroductionCanine infectious respiratory disease complex (CIRDC), widely known as kennel cough or infectious tracheobronchitis, is a highly contagious disease in dogs caused by multiple bacterial and viral pathogens. Two significant pathogens that contribute to CIRDC are Bordetella bronchiseptica (B. bronchiseptica) and canine parainfluenza virus (CPI). Recently, the first oral, modified live, vaccine to contain a combination of these two pathogens has become commercially available.MethodsTo evaluate the efficacy of both fractions of this vaccine, duration of immunity studies were conducted in six- to eight-week-old beagles. In both studies, dogs were randomized into two treatment groups and vaccinated once by the oral route with either test vaccine or placebo vaccine. In the CPI study, dogs were challenged with virulent CPI one year after vaccination and observed daily for 14 days post-challenge. Nasal swabs were also collected daily for 10 days post-challenge to evaluate the shedding of the challenge virus. In the B. bronchiseptica study, dogs were challenged with virulent B. bronchiseptica one year after vaccination and observed twice daily for 28 days post-challenge for clinical signs of disease.ResultsThe results from these studies demonstrated a significant reduction in nasal shedding of CPI (0.2 log10FAID50/mL in test-vaccinated compared to 1.1 log10FAID50/mL in placebo-vaccinated dogs) as well as a significant reduction in clinical signs associated with B. bronchiseptica (9% of test-vaccinated compared to 74% of placebo-vaccinated dogs).ConclusionTaken together, these studies demonstrated that oral vaccination with a combination vaccine containing B. bronchiseptica and CPI is effective at preventing disease for at least one year following vaccination.

ASFV-G-ΔI177L is a modified-live African swine fever virus (ASFV) strain that has been incorporated into a commercially available vaccine. Its safety in pregnant sows and genetic stability in an in vivo passaging experiment were investigated. Upon inoculation of two pregnant sows with ASFV-G-ΔI177L, one developed moderate ASF-related clinical signs. In terms of reproductive performance, 43% of the offspring was born dead and the live-born piglets developed ASF-specific clinical signs, became viremic, and only 17% survived until the end of study. During passaging in pigs, ASFV-G-ΔI177L reverted to virulence with severe ASF-specific clinical signs at passages 3 and 4, associated with increased viremia. Whole genome sequencing identified C257L mutations as a potential driver of increased replication fitness and virulence. The data show that ASFV-G-ΔI177L is not genetically stable and, therefore not safe for use in ASF vaccines and suggest that ASF vaccine candidates should be tested for safety in pregnant animals.

Cryptosporidium parvum (C. parvum)-caused calf diarrhoea (scours) is widespread and leads to calf mortality in cattle industries worldwide. A recent discovery of a glycopeptide epitope on the Cryptosporidium parasite recognized by a monoclonal antibody has led to the development of a new vaccine. It was designed for cows to pass on passive immunity to their neonatal calves. This vaccine has been demonstrated to be safe and efficacious in pre-clinical studies. In the process of marketing registration, two clinical studies were conducted with this vaccine on 16 commercial dairy and beef farms collecting data, assessed by the European Medicine Agency. In these studies, its effectiveness in the field was evaluated. The natural challenge and clinical disease caused by Cryptosporidium parvum in the calves in these studies was, however, not high enough to show a significant reduction of most of the clinical signs, although all trends were in favour of the vaccination groups. Nonetheless, the duration of the diarrhoea episodes of the dairy calves was significantly shorter in the vaccination group. Additionally, the levels of Gp40 antibodies in the blood of the calves was notably higher in the vaccination groups, demonstrating the principle of passive immunization. Overall, this vaccine, which can be used concurrently, non-mixed with Bovilis® Rotavec® Corona, introduces an additional approach to mitigate the impact of C. parvum infections in neonatal calves.

ABSTRACT Background A bivalent human papillomavirus vaccine (2vHPV) is currently used in the Netherlands; a nonavalent vaccine (9vHPV) is also licensed. Research design and methods We compared the public health and economic benefits of 2vHPV- and 9vHPV-based vaccination strategies in the Netherlands over 100 years using a validated deterministic dynamic transmission metapopulation model. Results Compared to 2vHPV, the 9vHPV strategy averted an additional 3,245 cases of and 825 deaths from 9vHPV-strain-attributable cancers, 4,247 cases of and 190 deaths from recurrent respiratory papillomatosis (RRP), and 1,009,637 cases of anogenital warts (AGWs), with an incremental cost-effectiveness ratio (ICER) of €4,975 per quality-adjusted life year (QALY) gained. The ICER increased in a scenario with increased HPV vaccination coverage rates and was relatively robust to one-way deterministic sensitivity analyses, with variation in the disease utility parameter having the most impact. When catch-up vaccination for individuals ≤26 years of age was added to the model, vaccinating with 9vHPV averted additional cancers and AGWs compared to 2vHPV vaccination. Conclusion Our analyses predict that transitioning from a 2vHPV- to a 9vHPV-based vaccination strategy would be cost-effective in the Netherlands.

Canine influenza virus (CIV) H3N2 causes a highly contagious respiratory disease in dogs and has been the source of outbreaks across North America since 2015. An injectable RNA Particle (RP)-CIV H3N2 vaccine has been developed to protect dogs against this disease. To demonstrate efficacy, dogs were randomized into two treatment groups, then vaccinated subcutaneously twice, 21 days apart, with a placebo vaccine (n = 20) or a RP-CIV H3N2 vaccine (n = 20). Three weeks later, dogs were challenged intranasally with virulent CIV H3N2 and observed daily for 10 days for clinical signs of disease. Nasal swabs were also collected daily to evaluate shedding of the challenge virus. Ten days post-challenge, dogs were euthanized, and the lungs were examined for consolidation. RP-CIV H3N2 vaccination demonstrated a significant reduction in duration of clinical signs, duration and amount of virus shed, lung consolidation, and the incidence of suppurative pneumonia. To evaluate safety, dogs from multiple geographic regions were vaccinated subcutaneously, 3-4 weeks apart, with a RP-CIV H3N2 vaccine and observed for adverse events for 14 days after each administration. The RP-CIV H3N2 vaccine was deemed safe, with lethargy being the most reported adverse event at a rate of 1.6%.