Stopping Vaccination Research Articles

Why Foot-and-Mouth Disease-Free with Vaccination Should Be Equivalent to Foot-and-Mouth Disease-Free without Vaccination.

Foot-and-Mouth Disease (FMD) is still one of the most relevant animal diseases and remains of global concern. The World Organization for Animal Health (WOAH) has specified two sanitary statuses that assure freedom from FMD: a country or zone can be free from FMD either with or without vaccination. To obtain either of the two statuses, absence of virus circulation must be shown. The standards set by WOAH are used for trade negotiations. During recent decades, different tools and approaches were developed to control FMD, including vaccines, diagnostics, and the Progressive Control Pathway for FMD. These tools improved over time, and nowadays high-quality, reliable vaccines and specific diagnostics are available to efficiently control and detect the infection, even in vaccinated populations. Due to these improvements, it is no longer justifiable to treat the two FMD-free statuses differently. The distinction between the statuses provides wrong incentives and tempts countries to take increased risks by stopping vaccination to improve their trade conditions, which can have potentially devastating consequences. The decision to stop vaccination should only be made on the basis of a careful and comprehensive analysis of the local and regional epidemiological situation. This paper presents the perspective that member countries and WOAH should recognize the two FMD-free statuses as equivalent.

¿Debemos dejar de vacunar contra Fiebre Aftosa en Uruguay? Una encuesta nacional a veterinarios Autores/as

Veterinarians’ opinions are key to successfully implementing disease control programs. Foot-and-mouth disease (FMD) has a significant economic impact due to animal production losses and trade restrictions. In 2010, PANAFTOSA defined a roadmap to FMD eradication in South America. Although Uruguay has implemented this plan by using mandatory vaccination since the last outbreak in 2001, vaccination restricts access to premium export markets. The objective of this study was to determine the perception of veterinarians involved in large animal disease control programs (accredited veterinarians) on a future FMD control stage without vaccination in Uruguay. Two hundred and fifty-six accredited veterinarians were surveyed between August and September 2018. Two strata were defined as follows: Stratum 1 (pre-FMD outbreak), veterinarians who enrolled in the University of the Republic in Uruguay before or in 2001 (N=708), and Stratum 2 (post-FMD outbreak) veterinarians who enrolled after 2001 (N=426). Data related to demographics, vaccination perceptions, and FMD experience were collected through online and phone interviews. Logistic regressions were used to determine the association between demographic variables, FMD-related risk perceptions, and the willingness to stop FMD vaccination. 41.7% (± 4.2) and 29.4% (± 4.2) of veterinarians, for strata 1 or 2, respectively, were willing to stop vaccination. Veterinarians’ geographical region of work influenced this perception. The northeast area being more likely to support stopping vaccination (46.3 ± 5.8%) when compared to the South-center (39.2 ± 4.9%) and West (25.3 ± 5.0%). Accredited veterinarians are still hesitant to stop vaccination, presenting problems when implementing a non-vaccination stage.

Newborn BCG vaccination complemented by boosting correlates better with reduced juvenile diabetes in females, than vaccination alone

Type 1 diabetes (T1D), like other autoimmune diseases, is on the rise since the second half of the 20th century. Hypothetically this has been ascribed to restricted exposure to microbial diversity due to advanced hygienic practices accompanying modernization, and increasing prosperity in urban versus rural habitats. The autoimmune animal model of T1D, inhibited by Bacillus Calmette Guerine (BCG), motivated testing the impact of BCG on T1D incidence in humans. Several epidemiological analyses, short of one, failed to demonstrate a protective effect of BCG against T1D. The present retrospective analysis of two data sets reevaluates the hypothetic inhibitory effect of BCG on human T1D. Reassessment of data from a Swedish study reveals that a single BCG vaccination provided a small but significant protection against T1D. A second data set of T1D prevalence/1000 Israeli military conscripts, from a doctoral thesis presenting 17 birth cohorts at age 17 is evaluated against the national schedule of vaccination related to years of birth. To correct for the annual increasing T1D trend the mean urbanization (census) rate was set as an annual moving average and factored into the prevalence (T1D/1000) of respective birth cohorts. Three groups of cohorts corresponding to BCG vaccination are presently identified; Group A corresponds to the years in which newborns were vaccinated and boosted if necessary, at age 12. Group B corresponds to the period when boosting was discontinued. Group C corresponds to years when newborn BCG vaccination was discontinued. T1D (only in females) was slightly but significantly lower in group B (n = 5 cohorts) versus C (n = 8 cohorts, p = 0.0475, by Mann Whitney U test). T1D in group A (n = 4 cohorts) was lower than in group B (p = 0.02). This analysis supports the hypothesis that in human females postnatal BCG vaccination, reinforced by boosting, has a protective impact on T1D being superior to omitted boosting, which in its turn is still better than stopping vaccination altogether. This analysis further suggests that upon advanced modernization the BCG vaccine compensates for reduced exposure to microbial diversity early in life.

Impacto de la vacuna neumocócica conjugada 13-valente en niños. Efecto de su retirada del calendario infantil de vacunación (Madrid)

ObjectiveIn June 2010, the Madrid autonomous community approved that the 13-valent pneumococcal conjugate vaccine (PCV13) replace PCV7 for routine administration to children. However in June 2012, was suppressed. The objective was to analyse the trends of invasive pneumococcal serotypes and antimicrobial resistances patterns in children in 2012-2014, particularly after the stopping vaccination of PCV13. MethodsDuring 2012-2014, 24 cases (24 patients) of invasive pneumococcal disease (IPD) were identified. Susceptibilities to penicillin and cefotaxime were determined by microdilution. The strains were sent for serotyping to Department of Microbiology of Hospital Clínico Universitario (Madrid). ResultsA total of 24 isolates of pneumococcus were made at Hospital Infantil Niño Jesús (Madrid), 22 in blood, one in cerebrospinal fluid, and one in pleural fluid. The highest rates of IPD were found in children aged 12-23months old and ≥36months. Distribution by clinical presentation was: 50% (12) primary bacteremia, 29% (7) bacteremic pneumonia, 13% (3) bacteremic meningitis, 4% (1) meningitis, 4% (1) empyema, and 4% (1) bacteremic pneumonia secondary to otitis. Seventy-eight percent of serotypes were non-PCV13. During the PCV13 universal vaccination period (January-May 2012), 4/6 isolates were non-PCV13 (10A, 23B, 8, 11A). During the PCV13 suppression period (from June 2012) 14/17 isolates were non-PCV13 (23B, 10A, 15A, 6C, 15B, 24F). All isolates were susceptible. ConclusionIn the population studied, the suppression of the PCV13 did not cause a rebound in the number of IPD for serotypes included. The PCV13 offers clear benefits as a preventive measure against IPD in children.

Strategies to increase influenza vaccination rates: outcomes of a nationwide cross-sectional survey of UK general practice

ObjectiveTo identify practice strategies associated with higher flu vaccination rates in primary care.DesignLogistic regression analysis of data from a cross-sectional online questionnaire.Setting795 general practices across England.Participants569 practice managers, 335 nursing...

Estimating the risk of re-emergence after stopping polio vaccination.

Live vaccination against polio has effectively prevented outbreaks in most developed countries for more than 40 years, and there remain only a few countries where outbreaks of poliomyelitis by the wild strain still threaten the community. It is expected that worldwide eradication will be eventually achieved through careful surveillance and a well-managed immunization program. The present paper argues, however, that based on a simple stochastic model the risk of outbreak by a vaccine-derived strain after the cessation of vaccination is quite high, even if many years have passed since the last confirmed case. As vaccinated hosts are natural reservoirs for virulent poliovirus, the source of the risk is the vaccination itself, employed to prevent the outbreaks. The crisis after stopping vaccination will emerge when the following two conditions are met: the susceptible host density exceeds the threshold for epidemics and the vaccinated host density remains large enough to ensure the occurrence of virulent mutants in the population. Our estimates for transmission, recovery, and mutation rates, show that the probability of an outbreak of vaccine-derived virulent viruses easily exceeds 90%. Moreover, if a small fraction of hosts have a longer infectious period, as observed in individuals with innate immunodeficiency, the risk of an outbreak rises significantly. Under such conditions, successful global eradication of polio is restricted to a certain range of parameters even if inactivated polio vaccine (IPV) is extensively used after the termination of live vaccination.

Erratum to “Unexpected High Response Rate to Traditional Therapy after Dendritic Cell-Based Vaccine in Advanced Melanoma: Update of Clinical Outcome and Subgroup Analysis”

We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8-33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16-61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.

Reducing financial barriers to vaccinating children and adolescents in the USA

To increase awareness of the financial barriers to childhood and adolescent vaccination, recent steps taken to mitigate these barriers, and remaining gaps following passage of Federal healthcare reform legislation. Financial barriers to vaccination remain, even with the safety net of the Vaccines for Children Program. Newly recommended vaccines have substantially increased the cost to fully vaccinate a child up to age 18 years, and the combination of these cost burdens and inadequate reimbursement, in both the private and public sectors, has led some physicians to seriously consider stopping vaccination services. Up to 20% of privately insured children or adolescents have coverage that does not fully cover all costs of immunization, potentially leading to fragmented and inadequate preventive care. Federal healthcare reform legislation, as currently constituted, may not fully address all financing gaps, and the extent to which financial barriers to immunization services remain will need to be evaluated as the legislation is implemented. Recent National Vaccine Advisory Committee recommendations need to be considered to address financial barriers to immunization.

Unexpected High Response Rate to Traditional Therapy after Dendritic Cell‐Based Vaccine in Advanced Melanoma: Update of Clinical Outcome and Subgroup Analysis

We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8–33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16–61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.

Dendritic cell vaccination in melanoma patients: Update and subgroup analysis of clinical response to post-vaccine treatment

9042 Background: Dendritic cells (DCs) play a crucial role in the interplay between innate and adaptive immune response towards cancer. The combination of immunotherapies with standard treatments for cancer could represent a further chance for advanced melanoma patients. In the literature, higher response rates than those normally obtained have been reported after second-line chemotherapy in patients with non small cell lung cancer pre-treated with vaccines and in patients with follicular B-cell lymphoma vaccinated with an anti-idiotype vaccine whilst in remission. On the basis of this data, we reviewed and updated the clinical results of our dendritic cell based vaccine clinical trial in stage IV melanoma patients. Methods: From December 2002 to 2007, 24 pre-treated metastatic melanoma patients were vaccinated with mature DCs (mDCs) pulsed with autologous tumor lysate (ATL) and keyhole limpet hemocyanin (KLH) followed by a 5-day treatment with low-dose subcutaneous Interleukin-2. Results: We observed 2 complete response (CR), 2 mixed response (MR), 5 partial response (PR), 4 stable disease (SD) and 11 progressive disease (PD) (overall response (OS) 37.5%; clinical benefit 54.1%). All 13 responders had delayed-type hypersensitivity (DTH) positivity to KLH, of whom 10 also showed positivity to the lysate. Eleven (45.8%) of the 24 patients underwent further lines of treatment (5 chemotherapy [CT], 3 surgery [S], 4 biotherapy, 2 radiotherapy [RT] and 4 biochemotherapy [BioCT]) after stopping vaccination (8 due to progression and 3, in SD, because all of their lysate had been used). Of these 11 patients, 2 obtained CR (1 RT, 1 S), 5 PR (3 BioCT, 2 S) for an OR of 63.6%, 1 SD (BioCT) and 3 showed PD as the best response to subsequent therapies, with a median OS of 30 months (range 16–52). Of the 3 SD patients who were forced to stop vaccine treatment, 1 had CR following RT and 2 progressed. Conclusions: Metastatic melanoma responds poorly to standard therapy, in particular after first-line treatment. Vaccination could enhance clinical response to subsequent third- or fourth-line therapies, thus prolonging overall survival. No significant financial relationships to disclose.

Rational Design of Genetically Stable, Live-Attenuated Poliovirus Vaccines of All Three Serotypes: Relevance to Poliomyelitis Eradication

The global eradication of poliomyelitis caused by wild-type virus is likely to be completed within the next few years, despite immense logistic and political difficulties, and may ultimately be followed by the cessation of vaccination. However, the existing live-attenuated vaccines have the potential to revert to virulence, causing occasional disease, and viruses can be shed by immunocompromised individuals for prolonged periods of time. Moreover, several outbreaks of poliomyelitis have been shown to be caused by viruses derived from the Sabin vaccine strains. The appearance of such strains depends on the prevailing circumstances but poses a severe obstacle to strategies for stopping vaccination. Vaccine strains that are incapable of reversion at a measurable rate would provide a possible solution. Here, we describe the constructions of strains of type 3 poliovirus that are stabilized by the introduction of four mutations in the 5' noncoding region compared to the present vaccine. The strains are genetically and phenotypically stable under conditions where the present vaccine loses the attenuating mutation in the 5' noncoding region completely. Type 1 and type 2 strains in which the entire 5' noncoding regions of Sabin 1 and Sabin 2 were replaced exactly with that of one of the type 3 strains were also constructed. The genetic stability of 5' noncoding regions of these viruses matched that of the type 3 strains, but significant phenotypic reversion occurred, illustrating the potential limitations of a rational approach to the genetic stabilization of live RNA virus vaccines.

Combined vaccination with idiotype-pulsed allogeneic dendritic cells and soluble protein idiotype for multiple myeloma patients relapsing after reduced-intensity conditioning allogeneic stem cell transplantation

Background and objective: To combine the use of idiotype-pulsed allogeneic dendritic cells (alloDC) and soluble protein Id conjugated with KLH (Id-KLH) in a vaccine strategy for multiple myeloma (MM).Design and methods: Four MM patients received the combined vaccine after having experienced disease relapse/progression following reduced intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) and failure to rescue therapy with donor lymphocyte infusion or chemotherapy (CHT).Results: Vaccination was well tolerated and induced an anti-KLH antibody response in all 4 patients as well as substantial cell proliferation. In contrast, no case showed similar effects against either tumor-specific Id or irrelevant isotype control immunoglobulins (Ig). In turn, vaccination was associated with modulation of biological responses linked to both inflammatory and T-cell activation, with secretion of effector Th1 cytokines. In particular, an important increase in the spontaneous ex vivo secretion of TNFα, IL-6 and IFNγ as well as IL-2 and IL-10 was frequently observed prior to the fourth vaccination. Moreover, in vitro stimulation with Id-KLH and Id-KLH plus alloDC, but not with alloDC alone was associated with an enhanced number of TNF-α+ T-cells and an increased secretion of IFNγ and IL-2 before the third and fourth vaccination. From a clinical standpoint, 2 patients had a transient response and 1 has stable disease after stopping vaccination, while 3 of them ultimately progressed.Interpretation and conclusions: The results show for the first time that the use of Id-pulsed alloDC following RIC alloSCT is safe and feasible. However, crucial strategy improvements are warranted to possibly achieve clinical benefit.

Aujeszky's disease virus eradication campaign successfully heading for last stage in the Netherlands

Summary The Aujeszky's disease virus (ADV) eradication campaign in the Netherlands is based on compulsory vaccination and certification of ADV‐free herds and consists of three stages: reduction of transmission of ADV, tracing and elimination of remaining sources of ADV, and, in the last stage prohibition of vaccination. This paper summarizes the progress made in the first two stages of the eradication. Between 1994–1999, ADV seroprevalence decreased sharply in all four regions in the Netherlands, both in the sow and the finishing pig population. In the sow population, the mean ADV prevalence in the northern, eastern and western regions decreased to less than 0.5% in the first quarter of 1998, and to approximately 1% in the southern region. For the finishing pig population, the mean ADV prevalence decreased to less than 0.6% in all fourregions in the first quarter of 1998. The proportion of sow herds that were certified ADV‐free increased steadily from approximately 40% in the last quarter of 1996 to 96% in the first quarter of 1999. The proportion of finishing pig herds that were certified ADV‐free showed the same spectacular increase as in the sow population: from approximately 14% in the last quarter of 1996 to 90% in the first quarter of 1999. It is anticipated that the last stage of the ADV eradication campaign, stopping vaccination, will be achieved very soon. Monitoring wild boars for ADV between 1994 and 1999 indicated that ADV is uncommon within the wild boar population. Therefore, it seems that ADV infection in the wild boar population is not an important reservoir in the Netherlands.

Stopping poliovirus vaccination after eradication: issues and challenges.

Since 1988 reported polio cases worldwide have declined by about 85% and the number of known or suspected polioendemic countries has decreased from over 120 to less than 50. With eradication of poliomyelitis approaching, issues potentially affecting when and how vaccination against poliovirus can be stopped become extremely important. Because of the potential risks and benefits inherent in such a decision, the best available science, a risk-benefit analysis, contingency plans, a stock pile of poliovirus vaccines, and the endorsement by the global policy-making committees will all be needed before vaccination can be discontinued. The scientific basis for stopping polio immunization has been reviewed by WHO. This Round Table article summarizes the current state of knowledge, provides an update on the processes and timelines for certification, containment, and stopping vaccination, and highlights some of the unanswered scientific questions that will be addressed by further research. These include whether transmission of vaccine-derived poliovirus strains could be sustained so that poliomyelitis could re-emerge in a future unvaccinated population and whether prolonged excretion of vaccine-derived poliovirus from individuals with immune deficiencies could be a mechanism through which this could occur.

Poliovirus vaccination: current understanding of poliovirus interactions in humans and implications for the eradication of poliomyelitis.

Poliomyelitis is a paralytic disease of the motor neurones of the central nervous system, which is caused by poliovirus. The virus is transmitted by the faecal-oral route, and if virus replication is confined to the gut, it is harmless. Poliomyelitis is an ancient human disease, but was rare until the beginning of the 20th century, when children began to be exposed to the virus at older ages and were, therefore, no longer protected by maternal antibody, which had already been lost. Inactivated polio vaccines are increasingly being used in those countries in which poliomyelitis has been brought under control; however, live vaccines are still the most widely used types and the World Health Organization (WHO) have set the goal of using such vaccines to eliminate the wild-type virus throughout the world by the year 2000. Substantial progress has been made to this end; however, the strains of poliovirus that are used as vaccines are able to adapt rapidly to the human gut, losing their attenuated (weakened) character within a few weeks. Currently, there is urgent debate about the best method of stopping vaccination against poliomyelitis once the wild-type poliovirus has been eliminated completely, so that the vaccine-strain virus will also be eliminated. Proposed strategies include the abrupt cessation of vaccination with the live virus worldwide, followed by the optional use of inactivated vaccines for an appropriate period. Further information about both the epidemiology and the pathogenesis of the disease is required before an informed choice can be made. The topics covered in this article include a brief history of studies of the disease, its pathogenesis and its control by vaccination, the molecular biology of the live vaccines, which have been extremely successful in controlling poliomyelitis so far, and the concerns that are raised as the eradication of the wild-type virus approaches.

Estimating incidence of whooping cough over time: a cross-sectional recall study of four Swedish birth cohorts.

Incidence of whooping cough was studied in Göteborg, Sweden, in four random samples of birth cohorts from 1972, 1977, 1978 and 1980. To obtain data a postal questionnaire to parents was used and methodologically explored. Vaccination data were taken from health cards. Four years after stopping vaccination cumulative incidence in the unvaccinated cohort born 1980 had risen to levels of the prevaccination era. Sex differences in susceptibility were not seen. Efficacy of the Swedish manufactured non-adsorbed whole cell pertussis vaccine was low. In a developed country like Sweden a cross-sectional study of random samples from the community with recall data may give useful information on the incidence of a disease like whooping cough at a comparatively low cost.