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A systematic review and network meta-analysis (MA) was conducted to address the question, ‘What is the efficacy of bacterial vaccines to prevent respiratory disease in swine?’ Four electronic databases and the grey literature were searched to identify clinical trials in healthy swine where at least one intervention arm was a commercially available vaccine for one or more bacterial pathogens associated with respiratory disease in swine, including Mycoplasma hyopneumoniae, Actinobacillus pleuropneumonia, Actinobacillus suis, Bordetella bronchiseptica, Pasteurella multocida, Stretococcus suis, Haemophils parasuis, and Mycoplasma hyorhinis. To be eligible, trials had to measure at least one of the following outcomes: incidence of clinical morbidity, mortality, lung lesions, or total antibiotic use. There were 179 eligible trials identified in 146 publications. Network MA was undertaken for morbidity, mortality, and the presence or absence of non-specific lung lesions. However, there was not a sufficient body of research evaluating the same interventions and outcomes to allow a meaningful synthesis of the comparative efficacy of the vaccines. To build this body of research, additional rigor in trial design and analysis, and detailed reporting of trial methods and results are warranted.
Vaccine effectiveness studies are subject to biases due to depletion-of-persons at risk of infection, or at especially high risk of infection, at different rates from different groups (depletion-of-susceptibles bias), a problem that can also lead to biased estimates of waning effectiveness, including spurious inference of waning when none exists. An alternative study design to identify waning is to study only vaccinated persons, and compare for each day the incidence in persons with earlier or later dates of vaccination to assess waning in vaccine protection as a function of vaccination time (namely whether earlier vaccination would result in lower subsequent protection compared to later vaccination). Prior studies suggested under what conditions this alternative would yield correct estimates of waning. Here we define the depletion-of-susceptibles process formally and show mathematically that for influenza vaccine waning studies, a randomised trial or corresponding observational study that compares incidence at a specific calendar time among individuals vaccinated at different times before the influenza season begins will not be vulnerable to depletion-of-susceptibles bias in its inference of waning as a function of vaccination time under the null hypothesis that none exists, and will – if waning does actually occur – underestimate the extent of waning. Such a design is thus robust in the sense that a finding of waning in that inference framework reflects actual waning of vaccine-induced immunity. We recommend such a design for future studies of waning, whether observational or randomised.
Vaccination coverage (VC) against pertussis can increase when management practices and policies at primary care centres (PCCs) are reinforced. From 2011 to 2015, we performed a case–control study to evaluate VC among pertussis patients treated at PCCs in Barcelona, Spain. We recorded pertussis in patients from 8- to 16-year-olds at 52 PCCs. Pertussis cases had laboratory diagnostic and controls were healthy outpatients visiting the same facility for reasons other than cough. DTaP/dTap VC was recorded as either proper vaccination status (five doses recorded) or improper vaccination status (<5 doses recorded). We used a logistic regression model to estimate OR and 95% CI. We included 229 cases and 576 controls. VC was higher in cases (mean 5.01, s.e.: 0.57) than in controls (4.89, s.e.: 0.73). Around 69% of the cases had received DTaP primary immunisation after 2–5 years and 31.4% of cases had the dTap booster immunisation after 7–10 years. The 87% of children 5–9 years were properly vaccinated. We found no protection from becoming ill among properly vaccinated children (OR 1.87; 95% CI 1.22–2.85). The highest VC was observed in patients with confirmed pertussis, which was likely due to a more exhaustive follow-up of the VC in these patients. Being properly vaccinated against pertussis will probably not increase VC.
Sustaining the impact of hepatitis B virus (HBV) vaccination on incidence and prevalence of HBV infection requires increasing and maintaining the uptake of vaccine among those at risk. In recent years, the level of vaccine uptake among people who inject drugs (PWID) in the UK has levelled-off. Data (2015–2016) from the national unlinked-anonymous monitoring survey of PWID, an annual survey that collects data from PWID across England, Wales and Northern Ireland, were used to examine HBV vaccine uptake. Data from participants who had injected drugs during the previous year were used to investigate sources of hepatitis B vaccine doses as well as factors associated with vaccine uptake. Among the 3175 anti-HBc-negative participants, 3138 (99%) reported their vaccination status; 23% (714) reported no vaccine uptake. Among those not vaccinated, 447 (63%) reported being sexually active and 116 (16%) reported sharing needles and syringes. Majority of those not vaccinated reported accessing services in the previous year that could have provided hepatitis B vaccine doses. These missed opportunities for vaccinating of PWID indicate a need for additional targeted interventions.
England has recently started a new paediatric influenza vaccine programme using a live-attenuated influenza vaccine (LAIV). There is uncertainty over how well the vaccine protects against more severe end-points. A test-negative case–control study was used to estimate vaccine effectiveness (VE) in vaccine-eligible children aged 2–16 years of age in preventing laboratory-confirmed influenza hospitalisation in England in the 2015–2016 season using a national sentinel laboratory surveillance system. Logistic regression was used to estimate the VE with adjustment for sex, risk-group, age group, region, ethnicity, deprivation and month of sample collection. A total of 977 individuals were included in the study (348 cases and 629 controls). The overall adjusted VE for all study ages and vaccine types was 33.4% (95% confidence interval (CI) 2.3–54.6) after adjusting for age group, sex, index of multiple deprivation, ethnicity, region, sample month and risk group. Risk group was shown to be an important confounder. The adjusted VE for all influenza types for the live-attenuated vaccine was 41.9% (95% CI 7.3–63.6) and 28.8% (95% CI −31.1 to 61.3) for the inactivated vaccine. The study provides evidence of the effectiveness of influenza vaccination in preventing hospitalisation due to laboratory-confirmed influenza in children in 2015–2016 and continues to support the rollout of the LAIV childhood programme.
We present a model to optimise a vaccination campaign aiming to prevent or to curb a Zika virus outbreak. We show that the optimum vaccination strategy to reduce the number of cases by a mass vaccination campaign should start when the Aedes mosquitoes' density reaches the threshold of 1.5 mosquitoes per humans, the moment the reproduction number crosses one. The maximum time it is advisable to wait for the introduction of a vaccination campaign is when the first ZIKV case is identified, although this would not be as effective to minimise the number of infections as when the mosquitoes' density crosses the critical threshold. This suboptimum strategy, however, would still curb the outbreak. In both cases, the catch up strategy should aim to vaccinate at least 25% of the target population during a concentrated effort of 1 month immediately after identifying the threshold. This is the time taken to accumulate the herd immunity threshold of 56.5%. These calculations were done based on theoretical assumptions that vaccine implementation would be feasible within a very short time frame.
During the 2009 influenza pandemic, a rapid assessment of disease severity was a challenge as a significant proportion of cases did not seek medical care; care-seeking behaviour changed and the proportion asymptomatic was unknown. A random-digit-dialling telephone survey was undertaken during the 2011/12 winter season in England and Wales to address the feasibility of answering these questions. A proportional quota sampling strategy was employed based on gender, age group, geographical location, employment status and level of education. Households were recruited pre-season and re-contacted immediately following peak seasonal influenza activity. The pre-peak survey was undertaken in October 2011 with 1061 individuals recruited and the post-peak telephone survey in March 2012. Eight hundred and thirty-four of the 1061 (78.6%) participants were successfully re-contacted. Their demographic characteristics compared well to national census data. In total, 8.4% of participants self-reported an influenza-like illness (ILI) in the previous 2 weeks, with 3.2% conforming to the World Health Organization (WHO) ILI case definition. In total, 29.6% of the cases reported consulting their general practitioner. 54.1% of the 1061 participants agreed to be re-contacted about providing biological samples. A population-based cohort was successfully recruited and followed up. Longitudinal survey methodology provides a practical tool to assess disease severity during future pandemics.
The present cross-sectional serosurvey constitutes the first effort to describe the varicella zoster virus (VZV) seroepidemiology in Serbia. An age-stratified serum bank of 3570 residual samples collected between 2015 and 2016 in each of the seven districts of the Vojvodina Province was tested for IgG anti-VZV antibodies with an enzyme immunoassay. Results were standardised into common units according to the European Sero-Epidemiology Network (ESEN2) methodology. Univariable and multivariable analyses were used to examine the relationships between standardised anti-VZV positivity or logarithmically transformed antibody titres and demographic features of study subjects. Seropositivity (85% overall) increased with age, in parallel with geometric mean titres. By the time of school entry, 68% of children were immune. The slower subsequent acquisition of immunity leaves epidemiologically relevant proportions of adolescents (7%), young adults (6%) and especially females of reproductive age (6%) prone to more severe forms of varicella. In the ongoing pre-vaccine era, natural infection provides a high level of collective immunity, with the highest VZV transmission in children of preschool age. The detected gaps in VZV immunity of the Serbian population support the adoption of the official recommendations for varicella immunisation of non-immune adolescents and young adults, including non-pregnant women of childbearing age.
Our objective was to identify predictors of severe acute respiratory infection in hospitalised patients and understand the impact of vaccination and neuraminidase inhibitor administration on severe influenza. We analysed data from a study evaluating influenza vaccine effectiveness in two Michigan hospitals during the 2014–2015 and 2015–2016 influenza seasons. Adults admitted to the hospital with an acute respiratory infection were eligible. Through patient interview and medical record review, we evaluated potential risk factors for severe disease, defined as ICU admission, 30-day readmission, and hospital length of stay (LOS). Two hundred sixteen of 1119 participants had PCR-confirmed influenza. Frailty score, Charlson score and tertile of prior-year healthcare visits were associated with LOS. Charlson score >2 (OR 1.5 (1.0–2.3)) was associated with ICU admission. Highest tertile of prior-year visits (OR 0.3 (0.2–0.7)) was associated with decreased ICU admission. Increasing tertile of visits (OR 1.5 (1.2–1.8)) was associated with 30-day readmission. Frailty and prior-year healthcare visits were associated with 30-day readmission among influenza-positive participants. Neuraminidase inhibitors were associated with decreased LOS among vaccinated participants with influenza A (HR 1.6 (1.0–2.4)). Overall, frailty and lack of prior-year healthcare visits were predictors of disease severity. Neuraminidase inhibitors were associated with reduced severity among vaccine recipients.
The Belgian strategic plan to eliminate measles contains several vaccination strategies including routine immunisation programmes and catch-up campaigns. A new expanded programme on immunisation-based survey (2016) assessed the uptake of the recommended measles–mumps–rubella (MMR) vaccine in three different cohorts: toddlers, adolescents and parents of toddlers. A two-stage cluster sampling technique was used to select 875 toddlers (age 18–24 months) and 1250 adolescents (born in 2000) from 107 municipalities in Flanders. After consent of the parent(s), 746 (85.2%) families of toddlers and 1012 (81.0%) families of adolescents were interviewed at home. Measles vaccination coverage was high at 18–24 months (96.2%) and 81.5% were vaccinated at recommended age. Toddlers who had two siblings or a non-working mother or changed vaccinator were more at risk for not being vaccinated. Coverage of the teenager dose reached 93.5% and was lower in adolescents with educational underachievement or whose mother was part-time working or with a non-Belgian background. Only 56.0% of mothers and 48.3% of fathers remembered having received at least one measles-containing vaccine. Although measles vaccination coverage in toddlers meets the required standards for elimination, administration of the teenager dose of MMR vaccine and parent compliance to the recent measles catch-up campaign in Flanders leave room for improvement.
Vaccination remains a mainstay of companion animal population health. However, how vaccine use at a population level complies with existing guidelines is unknown. Here we use electronic health records to describe vaccination in dogs, cats and rabbits attending a large sentinel network of UK veterinary practices. In total, 77.9% (95% CI: 77.6–78.1) of animals had recorded vaccinations. The percentage of animals with recorded vaccinations was higher in dogs, neutered animals, in insured dogs and cats and in purebred dogs. Vaccination rates varied in different regions of Great Britain in all species. Dogs and cats belonging to owners living in less deprived areas of England and Scotland were more likely to be recorded as vaccinated. In the vaccinated population, cats received more core vaccines per year of life (0.86) than dogs (0.75), with feline leukaemia vaccines almost as frequent as core vaccines. In dogs, leptospira vaccines were more frequent than core vaccines. This descriptive study suggests a substantial proportion of animals are not benefiting from vaccine protection. For the first time, we identify potential factors associated with variations in recorded vaccination frequency, providing a critical baseline against which to monitor future changes in companion animal vaccination and evidence to inform future targeted health interventions.
In Hong Kong, universal varicella vaccination started in July 2014. Before this, children could receive varicella vaccine via the private market. We analysed the epidemiology of varicella and zoster before universal vaccination. We estimated varicella vaccination coverage through surveys in preschool children. We estimated the burden of varicella and zoster with varicella notifications from 1999/00 to 2013/14, Accident and Emergency Department (A&E) attendance and inpatient admissions to public hospitals from 2004/05 to 2013/14. We fitted a catalytic model to serological data on antibodies against varicella-zoster virus to estimate the force of infection. We found that varicella vaccination coverage gradually increased to about 50% before programme inception. In children younger than 5 years, the annual rate of varicella notifications, varicella admission and zoster A&E attendance generally declined. The annual notification, A&E attendance and hospitalisation rate of varicella and zoster generally increased for individuals between 10 and 59 years old. Varicella serology indicated an age shift during the study period towards a higher proportion of infections in slightly older individuals, but the change was most notable before vaccine licensure. In conclusion, we observed a shift in the burden of varicella to slightly older age groups with a corresponding increase in incidence but it cannot necessarily be attributed to private market vaccine coverage alone. Increasing varicella vaccination uptake in the private market might affect varicella transmission and epidemiology, but not to the level of interrupting transmission.
Dendritic cells (DC) are central regulators of immune responses and professional antigen-presenting cells (APCs) with the unique ability to induce both innate immune responses and a highly specific acquired immunity. DC communicates through chemical and mechanical signals in the initiation and maintenance of immune responses. DC forms immunological synapses with T-cells thus pulling T-cells strings and leading to activation of T-cells. Owing to their properties, DC are often called ‘nature's adjuvants’ and thus have become an important component of any vaccination strategy. Coccidiosis is a major intestinal disease caused by Eimeria spp., affecting economically valuable livestock animals such as chickens and turkeys. Economic losses are associated with decreased productivity in afflicted poultry. Vaccination strategies involving DC have been developed owing to the special properties of these cells in coordinating innate and adaptive immune responses. Vaccination of chickens with exosomes isolated from DC containing parasite antigens (Ags) represents a promising alternative strategy to control avian coccidiosis. In recent years, emergence of new chicken DC has opened a new horizon for the development of new vaccines and DC derived vaccine could be a possible strategy to control coccidiosis in field. This review summarises the current state of knowledge of DC and their specific functions in immunity against avian coccidiosis.
The specific humoral immune response of sea bream, Sparus aurata (L.), against Vibrio anguillarum O1 and Photobacterium damselae subsp. piscicida (Phdp) after immunization with commercial and experimental bacterins was analysed quantitatively and qualitatively. Specific anti-V. anguillarum O1 and anti-Phdp levels provoked by the adjuvanted commercial vaccine reached higher levels in comparison to the aqueous commercial and experimental bacterins. Infection of vaccinated fish with V. anguillarum O1 bacterial cells acted as a boost of the humoral immune response, except for the sera of the group vaccinated with the adjuvanted vaccine. Infection with Phdp acted as a boost of the humoral immune response mainly for the group vaccinated with a monovalent Phdp bacterin and to a lesser degree for the group vaccinated with the aqueous commercial vaccine. Western blot analysis of the sera against V. anguillarum O1 whole cell antigens revealed strong reactions to only a few antigens below 54 kD and above 15 kD and weak reactions to other antigens. Similar reactions were observed from the sera isolated from the controls. Western blot analysis of the sera against Phdp whole cell antigens revealed strong reactions to only a handful of antigens below 20.7 and below 6.4 kD. Sera from the control group, as in the case of V. anguillarum O1, reacted with Phdp whole cell antigens. No differences regarding antigen reactions between monovalent and bivalent formulations were noted, in contrast to the adjuvanted and aqueous bacterins.
Effective tools for male contraception are important in the control of reproduction in animal populations. The aim of the present study was to evaluate the effects of active immunization against gonadotropin-releasing hormone (GnRH) on male reproductive function assessing testicular morphological changes and serum-gonadotropin levels in pre-pubertal rabbits, guinea pigs and ram lambs. An anti-GnRH vaccine was developed by linking a GnRH-homologous molecule to a tetanus clostridial toxoid (Al(OH)3 coadjuvant). After vaccination protocols testicular morphometry, histopathological alterations and endocrine responses (FSH, LH, testosterone and cortisol serum levels) were evaluated. Testicular volume was significantly reduced in vaccinated animals with respect to the control group in rabbits, guinea pigs and ram lambs (P<0.05 to P<0.001). The anti-GnRH vaccine generated a reduction in testicular volume of 15-, 27- and 11-fold, respectively. Tubule diameters decreased in the vaccinated group with respect to the control ~2.0-, 1.2- and 3.5-fold, respectively (P<0.001). Tubule, intertubular and lumen volumes significantly decreased in vaccinated rabbits (P<0.05), guinea pigs and ram lambs (P<0.01). Vaccinated animals of the three species showed significant reductions in spermatogonial numbers (10- to 40-fold; P<0.01). Sperm was absent in all seminiferous tubules of all rabbits, and most individuals of guinea pigs (80%) and ram lambs (60%). No significant differences were observed between vaccinated and control groups regarding FSH and LH during the experiments in the three experimental species/models used. Testosterone, however, was only significantly lower (~22-fold, P<0.01) in vaccinated rabbits. In conclusion, the present study demonstrated that pre-pubertal active immunization against GnRH leads to endocrine disruption and marked differences on testicular morphometry, development and activity among lagomorphs, hystricomorphs and ovine species with species-specific sensitivity regarding the anti-GnRH immune response.
Soil-transmitted helminths (STHs) collectively infect one fourth of all human beings, and the majority of livestock in the developing world. These gastrointestinal nematodes are the most important parasites on earth with regard to their prevalence in humans and livestock. Current anthelmintic drugs are losing their efficacies due to increasing drug resistance, particularly in STHs of livestock and drug treatment is often followed by rapid reinfection due to failure of the immune system to develop a protective response. Vaccines against STHs offer what drugs cannot accomplish alone. Because such vaccines would have to be produced on such a large scale, and be cost effective, recombinant subunit vaccines that include a minimum number of proteins produced in relatively simple and inexpensive expression systems are required. Here, we summarize all of the previous studies pertaining to recombinant subunit vaccines for STHs of humans and livestock with the goal of both informing the public of just how critical these parasites are, and to help guide future developments. We also discuss several key areas of vaccine development, which we believe to be critical for developing more potent recombinant subunit vaccines with broad-spectrum protection.
Dendritic cells (DCs) are antigen-presenting cells (APCs) with the unique ability to induce both innate immune responses and a highly specific acquired immunity. DCs are crucial to induce immunity, and their maturation and functions are influenced by microbial and environmental stimuli. Chicken DCs are composed of several subtypes including bursal secretory dendritic cells (BSDCs), follicular dendritic cells (FDCs), and thymic dendritic cells (TDCs). DC maturation depends on the nature of the perturbation and permits unique and efficient immune responses for each pathogen. DCs differentially recognise the viruses, bacteria, parasite and fungi and specifically regulate the immune response. Dendritic cells (DCs) are ‘nature's adjuvants’ and, as such represent an essential component of any vaccination strategy. The understanding of DC regulatory mechanisms opens a new horizon for the development of new vaccines and their targeting with the vaccination for elicitation of better immunity levels. The following review summarises the current state of knowledge of DCs and their specific functions during host pathogens interaction.
Every year the growth of the poultry industry is severely threatened by a number of infectious viral, bacterial and parasitic diseases. There are a number of vaccines to control these diseases including inactivated virus vaccines, attenuated virus vaccines, live virus vaccines, and subunit vaccines, but they are often relatively expensive and require cold storage and trained people to administer them, especially in developing countries. Plant-based vaccines provide a better option to control these diseases in low profit margin poultry industry. Still there are some challenges in the field of plant-based, so called ‘green’ vaccines. Injection-based oral priming is a big challenge for commercialisation of green vaccines so, new techniques are needed in the field of plant-based vaccine to pass these barriers for commercialisation. This discusses the potential for plant-based vaccines and whether they are good option to control poultry diseases.
Public health preparedness is an ever-evolving area of medicine with the purpose of helping the masses quickly and efficiently. The drive-through clinic (DTC) model allows the distribution of supplies or services while participants remain in their cars. Influenza vaccination is the most common form of DTC and has been utilized successfully in metropolitan areas.
We hypothesized that combining influenza vaccinations and child passenger seat fittings in a DTC format would be both feasible and desired by the community. Each driver was verbally surveyed at each DTC station. The project was a combination of patient survey and observation.
In the inaugural 6-hour DTC session, 86 cars were served and contained 161 children, of which 28 also participated in child passenger seat fittings. The median total clinic time regardless of services rendered was 9.0 minutes (interquartile range [IQR]: 6.0, 14.0 minutes). For those who received only an influenza vaccine, the median total time was 7.5 minutes (IQR: 6.0, 10.0 minutes). For those who received both services, the median total time was 27 minutes (IQR: 22.3, 33.5 minutes) with an average of 1.75 child passenger seat fittings per automobile.
This was a pilot study involving 2 different services using the DTC model and the first of its kind in the literature. The DTC was successful in executing both services without sacrificing speed, convenience, or patient satisfaction. Additional studies are needed to further evaluate the efficacy of the multiple-service DTC model. (Disaster Med Public Health Preparedness. 2017;11:647–651)
Vaccination has reduced rotavirus hospitalizations by 25% in European regions with low–moderate vaccine availability. We aimed to quantify the reduction in hospital costs after the longest period in which Rotarix® and Rotateq® were simultaneously commercially available in Spain. Cases, length of stay (LOS), and diagnosis-related groups (DRGs) were retrieved from the Minimum Basic Data Set. Healthcare expenditure was estimated through the cost accounting system Gescot®. DRGs were clustered: I, non-bacterial gastroenteritis with complications; II, without complications; III, requiring surgical/other procedures or neonatal cases (highest DRG weights). Comparisons between pre (2003–2005)- and post-vaccine (2007–2009) hospital stays and costs by DRG group were made. Rotaviruses were the most common agents of specific-coded gastroenteritis (N = 1657/5012). LOS and extended LOS of rotaviruses fell significantly in 2007–2009 (β-coefficient = −0·43, 95% confidence intervals (95% CI) −0·68 to −0·17; and odds ratio 0·62, 95% CI 0·50–0·76, respectively). Overall, costs attributable to rotavirus hospitalizations fell approximately €244 per patient (95% CI −365 to −123); the decrease in DRG group III was €2269 per patient (95% CI −4098 to −380). We concluded modest savings in hospital costs, largely attributable to cases with higher DRG weights, and a faster recovery. A universal rotavirus vaccination program deserves being re-evaluated, regarding its potential high impact on both at-risk children and societal costs.