Low Vaccine Efficacy Research Articles

Interfering with influenza: nonlinear coupling of reactive and static mitigation strategies.

When new, highly infectious strains of influenza emerge, global pandemics can occur before an effective vaccine is developed. Without a strain-specific vaccine, pandemics can only be mitigated by employing combinations of low-efficacy pre-pandemic vaccines and reactive response measures that are carried out as the pandemic unfolds. Unfortunately, the application of reactive interventions can lead to unintended consequences that may exacerbate unpredictable spreading dynamics and cause more drawn-out epidemics. Here, we employ a detailed model of pandemic influenza in Australia to simulate the combination of pre-pandemic vaccination and reactive antiviral prophylaxis. This study focuses on population-level coupling effects between the respective methods, and the associated spatio-temporal fluctuations in pandemic dynamics produced by reactive strategies. Our results show that combining strategies can produce either mutual improvement of performance or interference that reduces the effectiveness of each strategy when they are used together. We demonstrate that these coupling effects between intervention strategies are extremely sensitive to delay times, compliance rates and the type of contact targeting used to administer prophylaxis.

Low efficacy of vaccination against serogroup B meningococci in patients with atypical hemolytic uremic syndrome.

Background: The C5 complement inhibitor eculizumab is first-line treatment in atypical hemolytic uremic syndrome (aHUS) going along with a highly increased risk of meningococcal infections. Serogroup B meningococci (MenB) are the most frequently encountered cause for meningococcal infections in Europe. Efficacy of the protein-based MenB-vaccine Bexsero in aHUS has not been determined and testing is only possible in patients off-treatment with eculizumab as a human complement source is required.Methods: Patients with aHUS were vaccinated with two doses of the protein-based MenB-vaccine Bexsero. Serum bactericidal antibody (SBA) titers against factor H binding protein (fHbp) of MenB were determined in 14 patients with aHUS off-treatment with eculizumab.Results: Only 50% of patients showed protective human serum bactericidal antibody (hSBA) titers (≥1:4) against MenB following two vaccinations. Bactericidal antibody titers were relatively low (≤1:8) in three of seven patients with protective titers. While 71% of patients were on immunosuppressive treatment for either thrombotic microangiopathy or renal transplantation at either first or second vaccination, all four patients not receiving any immunosuppressive treatment showed protective bactericidal antibody response. Time between second vaccination and titer measurement was not significantly different between patients with protective titers compared with those with non-protective titers, while time between first and second vaccination was significantly longer in patients with protective titers going along with a tendency for reduction in immunosuppressive treatment.Conclusions: Efficacy of vaccination against MenB is insufficient in patients with aHUS. Response to vaccination seems to be hampered by immunosuppression. Therefore, implementation of adequate antibiotic prophylaxis seems pivotal.

Modelling the daily risk of Ebola in the presence and absence of a potential vaccine.

Ebola virus — one of the deadliest viral diseases, with a mortality rate around 90% — damages the immune system and organs, with symptoms including episodic fever, chills, malaise and myalgia. The Recombinant Vesicular Stomatitis Virus-based candidate vaccine (rVSV-ZEBOV) has demonstrated clinical efficacy against Ebola in ring-vaccination clinical trials. In order to evaluate the potential effect of this candidate vaccine, we developed risk equations for the daily risk of Ebola infection both currently and after vaccination. The risk equations account for the basic transmission probability of Ebola and the lowered risk due to various protection protocols: vaccination, hazmat suits, reduced contact with the infected living and dead bodies. Parameter space was sampled using Latin Hypercube Sampling, a statistical method for generating a near-random sample of parameter values. We found that at a high transmission rate of Ebola (i.e., if the transmission rate is greater than 90%), a large fraction of the population must be vaccinated (>80%) to achieve a 50% decrease in the daily risk of infection. If a vaccine is introduced, it must have at least 50% efficacy, and almost everyone in the affected areas must receive it to effectively control outbreaks of Ebola. These results indicate that a low-efficacy Ebola vaccine runs the risk of having vaccinated people be overconfident in a weak vaccine and hence the possibility that the vaccine could make the situation worse, unless the population can be sufficiently educated about the necessity for high vaccine uptake.

Vaccine Efficacy Induced by 2009 Pandemic H1N1 Virus-Like Particles Differs from that Induced by Split Influenza Virus

ABSTRACT Influenza virus-like particles (VLPs) vaccines are highly immunogenic, showing strong protective efficacy against homologous virus infection compared to split vaccine. However, a comparative efficacy study against heterosubtypic virus infection between VLPs and split vaccine has yet to been reported. In this study, we generated VLPs vaccine containing hemagglutinin (HA) and matrix protein (M1) of the 2009 pandemic H1N1, and investigated the protective efficacies induced by VLPs vaccine and commercial monovalent H1N1 pandemic split vaccine from Sanofi-Pasteur. Mice were intramuscularly immunized with either VLPs vaccine or split vaccine and subsequently challenge-infected with homologous virus (A/California/04/2009, H1N1) or heterosubtypic virus (A/Philippines/82, H3N2) after 4.5 months. VLPs vaccination demonstrated a higher level of protective efficacy against homologous viruses compared to split vaccine, as lessened lung viral loads and minuscule levels of proinflammatory lung cytokines IFN-gamma and IL-6 were observed. Protective efficacies were close to non-existent in VLP-immunized mice challenged with heterosubtypic viruses (H3N2). In contrast, split vaccine showed lower vaccine efficacy against homologous virus than VLP vaccine, but conferred better protection against heterosubtypic viruses through lung viral loads reduction and heightened survival rate. These results indicate that influenza VLPs provide better protective efficacy against homologous virus challenge infection, whereas split vaccine shows better protective efficacy against heterosubtypic virus challenge. Findings from the current study contribute to the rational design of vaccines conferring a broad range of protection.

Mincle and STING-Stimulating Adjuvants Elicit Robust Cellular Immunity and Drive Long-Lasting Memory Responses in a Foot-and-Mouth Disease Vaccine.

Conventional foot-and-mouth disease (FMD) vaccines exhibit several limitations, such as the slow induction of antibodies, short-term persistence of antibody titers, as well as low vaccine efficacy and safety, in pigs. Despite the importance of cellular immune response in host defense at the early stages of foot-and-mouth disease virus (FMDV) infection, most FMD vaccines focus on humoral immune response. Antibody response alone is insufficient to provide full protection against FMDV infection; cellular immunity is also required. Therefore, it is necessary to design a strategy for developing a novel FMD vaccine that induces a more potent, cellular immune response and a long-lasting humoral immune response that is also safe. Previously, we demonstrated the potential of various pattern recognition receptor (PRR) ligands and cytokines as adjuvants for the FMD vaccine. Based on these results, we investigated PRR ligands and cytokines adjuvant-mediated memory response in mice. Additionally, we also investigated cellular immune response in peripheral blood mononuclear cells (PBMCs) isolated from cattle and pigs. We further evaluated target-specific adjuvants, including Mincle, STING, TLR-7/8, and Dectin-1/2 ligand, for their role in generating ligand-mediated and long-lasting memory responses in cattle and pigs. The combination of Mincle and STING-stimulating ligands, such as trehalose-6, 6′dibehenate (TDB), and bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP), induced high levels of antigen-specific and virus-neutralizing antibody titers at the early stages of vaccination and maintained a long-lasting immune memory response in pigs. These findings are expected to provide important clues for the development of a robust FMD vaccine that stimulates both cellular and humoral immune responses, which would elicit a long-lasting, effective immune response, and address the limitations seen in the current FMD vaccine.

Extended delivery of vaccines to the skin improves immune responses

Vaccines prevent 2–3 million childhood deaths annually; however, low vaccine efficacy and the resulting need for booster doses create gaps in immunization coverage. In this translational study, we explore the benefits of extended release of licensed vaccine antigens into skin to increase immune responses after a single dose in order to design improved vaccine delivery systems. By administering daily intradermal injections of inactivated polio vaccine according to six different delivery profiles, zeroth-order release over 28 days resulted in neutralizing antibody titers equivalent to two bolus vaccinations administered one month apart. Vaccinations following this profile also improved immune responses to tetanus toxoid and subunit influenza vaccine but not a live-attenuated viral vaccine, measles vaccine. Finally, using subunit influenza vaccine, we demonstrated that daily vaccination by microneedle patch induced a potent, balanced humoral immunity with an increased memory response compared to bolus vaccination. We conclude that extended presentation of antigen in skin via intradermal injection or microneedle patch can enhance immune responses and reduce the number of vaccine doses, thereby enabling increased vaccination efficacy.

Molecular characterization of influenza viruses from women and infants in Sarlahi, Nepal

We used RT-PCR-electrospray ionization-mass spectrometry to identify subtypes and strains of influenza viruses detected during a maternal influenza immunization study in Nepal from May 2011 to April 2014. Hemagglutinin (HA) gene amino acid (aa) sequences of inferred reference strains were compared to those of the vaccines to determine impact of aa relatedness on vaccine efficacy (VE) and disease severity. Three influenza subtypes and many strains were identified. A(H3N2) strains with less than 13 aa differences in HA compared to vaccine strains (matched) showed higher VE than strains with 13 or more differences (mismatched). Yamagata lineage B strains, which were mismatched to the Victoria strain in the vaccine, demonstrated lower VE compared to Victoria strains. Differences in VE were not statistically significant. All A(H1N1pdm) matched the vaccine strain, with 10 or fewer aa differences. Except for women infected with vaccine-matched strains of influenza A, clinical signs and symptoms did not differ between vaccinated and unvaccinated participants.

The impact and cost-effectiveness of controlling cholera through the use of oral cholera vaccines in urban Bangladesh: A disease modeling and economic analysis.

BackgroundCholera remains an important public health problem in major cities in Bangladesh, especially in slum areas. In response to growing interest among local policymakers to control this disease, this study estimated the impact and cost-effectiveness of preventive cholera vaccination over a ten-year period in a high-risk slum population in Dhaka to inform decisions about the use of oral cholera vaccines as a key tool in reducing cholera risk in such populations.Methodology/Principal findingsAssuming use of a two-dose killed whole-cell oral cholera vaccine to be produced locally, the number of cholera cases and deaths averted was estimated for three target group options (1–4 year olds, 1–14 year olds, and all persons 1+), using cholera incidence data from Dhaka, estimates of vaccination coverage rates from the literature, and a dynamic model of cholera transmission based on data from Matlab, which incorporates herd effects. Local estimates of vaccination costs minus savings in treatment costs, were used to obtain incremental cost-effectiveness ratios for one- and ten-dose vial sizes. Vaccinating 1–14 year olds every three years, combined with annual routine vaccination of children, would be the most cost-effective strategy, reducing incidence in this population by 45% (assuming 10% annual migration), and costing was $823 (2015 USD) for single dose vials and $591 (2015 USD) for ten-dose vials per disability-adjusted life year (DALY) averted. Vaccinating all ages one year and above would reduce incidence by >90%, but would be 50% less cost-effective ($894–1,234/DALY averted). Limiting vaccination to 1–4 year olds would be the least cost-effective strategy (preventing only 7% of cases and costing $1,276-$1,731/DALY averted), due to the limited herd effects of vaccinating this small population and the lower vaccine efficacy in this age group.Conclusions/SignificanceProviding cholera vaccine to slum populations in Dhaka through periodic vaccination campaigns would significantly reduce cholera incidence and inequities, and be especially cost-effective if all 1–14 year olds are targeted.

THE SYSTEMATIC REVIEW OF EMPIRICAL RESEARCH OF FACTORS OF REFUSAL FROM VACCINATION

The worldwide reduction of vaccination uptake due to the voluntary refusal by some subpopulations constitutes a significant threat to public health. The study aims to provide systematic description of the factors which influence attitudes or behaviors associated with a vaccination rejection. A systematic review was carried out in 2015 using the Web of Science database. The analysis included English-language articles published from 1980 to 2015 containing the results of original empirical research of the phenomenon of refusal of vaccination. Of the 679 records found 30 publications met the inclusion criteria. The results showed that the determination of non-vaccination is extremely variable. All factors refusal of vaccination discovered in the research were divided into four content blocks: 1) demographics and socioeconomic status; 2) cognitive; 3) behavioral and 4) other factors (a) vaccine-specific, b) health and medical conditions, c) social environment, d) informational influence. The active studying the vaccination refusal as a socio-psychological phenomenon last for about 15 years, the majority of studies performed in the United States and Canada. In more than 5 independent studies there were found links of non-vaccination attitudes or behavior to the following factors: the perceived low vaccine efficacy (cognitive factor); the idea of a high probability of serious side effects of vaccination and general vaccines unsafety (cognitive factor); low level of trust to "official" medicine and public entities (cognitive factor); use of complementary and alternative medicine by family members (behavioral factors). Other potentially important factors found in 5 studies were: low perceived risk of vaccine preventable diseases and the perceived potential harm of vaccination to the immune system of the child (cognitive factors). The systematic review revealed a general underestimation of the social and psychological factors in the study of the phenomenon of non-vaccination and an emphasis on cognitive factors.

Optimizing the impact of low-efficacy influenza vaccines

The efficacy of influenza vaccines varies from one year to the next, with efficacy during the 2017-2018 season anticipated to be lower than usual. However, the impact of low-efficacy vaccines at the population level and their optimal age-specific distribution have yet to be ascertained. Applying an optimization algorithm to a mathematical model of influenza transmission and vaccination in the United States, we determined the optimal age-specific uptake of low-efficacy vaccine that would minimize incidence, hospitalization, mortality, and disability-adjusted life-years (DALYs), respectively. We found that even relatively low-efficacy influenza vaccines can be highly impactful, particularly when vaccine uptake is optimally distributed across age groups. As vaccine efficacy declines, the optimal distribution of vaccine uptake shifts toward the elderly to minimize mortality and DALYs. Health practitioner encouragement and concerted recruitment efforts are required to achieve optimal coverage among target age groups, thereby minimizing influenza morbidity and mortality for the population overall.

Assessing the Economic Impact of Vaccine Availability When Controlling Foot and Mouth Disease Outbreaks.

Predictive models have been used extensively to assess the likely effectiveness of vaccination policies as part of control measures in the event of a foot and mouth disease (FMD) outbreak. However, the availability of vaccine stocks and the impact of vaccine availability on disease control strategies represent a key uncertainty when assessing potential control strategies. Using an epidemiological, spatially explicit, simulation model in combination with a direct cost calculator, we assessed how vaccine availability constraints may affect the economic benefit of a “vaccination-to-live” strategy during a FMD outbreak in Scotland, when implemented alongside culling of infected premises and dangerous contacts. We investigated the impact of vaccine stock size and restocking delays on epidemiological and economic outcomes. We also assessed delays in the initial decision to vaccinate, maximum daily vaccination capacity, and vaccine efficacy. For scenarios with conditions conducive to large outbreaks, all vaccination strategies perform better than the strategy where only culling is implemented. A stock of 200,000 doses, enough to vaccinate 12% of the Scottish cattle population, would be sufficient to maximize the relative benefits of vaccination, both epidemiologically and economically. However, this generates a wider variation in economic cost than if vaccination is not implemented, making outcomes harder to predict. The probability of direct costs exceeding £500 million is reduced when vaccination is used and is steadily reduced further as the size of initial vaccine stock increases. If only a suboptimal quantity of vaccine doses is initially available (100,000 doses), restocking delays of more than 2 weeks rapidly increase the cost of controlling outbreaks. Impacts of low vaccine availability or restocking delays are particularly aggravated by delays in the initial decision to vaccinate, or low vaccine efficacy. Our findings confirm that implementing an emergency vaccination-to-live strategy in addition to the conventional stamping out strategy is economically beneficial in scenarios with conditions conducive to large FMD outbreaks in Scotland. However, the size of the initial vaccine stock available at the start of the outbreak and the interplay with other factors, such as vaccine efficacy and delays in restocking or implementing vaccination, should be considered in making decisions about optimal control strategies for FMD outbreaks.

Efficacy and Effectiveness of Rotavirus Vaccine on Incidence of Diarrhoea among Children: A Meta-analysis

Background: Introduction of rotavirus vaccines has resulted in a decrease in rotavirus related mortality and morbidity. We sought to conduct a meta-analysis to estimate the effect of rotavirus vaccine on incidence of diarrhoea. Methods: The MEDLINE database was searched through PubMed interface using both textword and subject headings (MeSH). The search strategies were [“rotavirus vaccine effectiveness” or “rotavirus vaccine efficacy” or “rotavirus vaccine eff*”]. The reference lists of the most recent studies identified by the search were checked for additional studies (if not already retrieved). We included both randomised trials and observational studies, which investigated the effect of rotavirus vaccine on incidence of diarrhoea. Results: There was strong evidence of vaccine efficacy (70%) on incidence of diarrhoea (Pooled risk ratio (pRR)=0.30; 95% confidence interval (CI)=(0.24,0.38); p<0.0001), with much lower vaccine efficacy (63%) in low-middle income countries (LMICs) (pRR=0.37; 95% CI=(56,69); p<0.0001). When restricted to severe diarrhoea outcome, we found 74% vaccine efficacy (pRR=0.26; 95% CI=(0.19,0.24); p<0.0001). For vaccine effectiveness in LMICs, we found 53% vaccine effectiveness (pRR=0.47; 95% CI=(0.36, 0.62); p<0.0001) for 1 dose; 61% effectiveness (pRR=0.39; 95% CI=(0.32, 0.47); p<0.0001) for 2 doses and 72% effectiveness (pRR=0.28; 95% CI=(0.14, 0.56); p<0.0001) for 3 doses. Conclusion: Incomplete dose series had lower vaccine effectiveness than vaccine efficacy in LMICs where health system capacity is low. However, a 3-dose series had similar effectiveness to vaccine efficacy, suggesting that a booster dose could present a potential benefit in LMIC.

Cost-Effectiveness of Dengue Vaccination Programs in Brazil.

The first approved dengue vaccine, CYD-TDV, a chimeric, live-attenuated, tetravalent dengue virus vaccine, was recently licensed in 13 countries, including Brazil. In light of recent vaccine approval, we modeled the cost-effectiveness of potential vaccination policies mathematically based on data from recent vaccine efficacy trials that indicated that vaccine efficacy was lower in seronegative individuals than in seropositive individuals. In our analysis, we investigated several vaccination programs, including routine vaccination, with various vaccine coverage levels and those with and without large catch-up campaigns. As it is unclear whether the vaccine protects against infection or just against disease, our model incorporated both direct and indirect effects of vaccination. We found that in the presence of vaccine-induced indirect protection, the cost-effectiveness of dengue vaccination decreased with increasing vaccine coverage levels because the marginal returns of herd immunity decreases with vaccine coverage. All routine dengue vaccination programs that we considered were cost-effective, reducing dengue incidence significantly. Specifically, a routine dengue vaccination of 9-year-olds would be cost-effective when the cost of vaccination per individual is less than $262. Furthermore, the combination of routine vaccination and large catch-up campaigns resulted in a greater reduction of dengue burden (by up to 93%) than routine vaccination alone, making it a cost-effective intervention as long as the cost per course of vaccination is $255 or less. Our results show that dengue vaccination would be cost-effective in Brazil even with a relatively low vaccine efficacy in seronegative individuals.

Determinants of influenza vaccination among solid organ transplant recipients attending Sicilian reference center

ABSTRACTAmong solid organ transplant recipients, influenza infection is commonly associated with higher morbidity and mortality than immunocompetent hosts. Therefore, in these subjects influenza vaccination is of paramount importance. The main objective of the study was to assess compliance to vaccination and analyze factors associated with influenza vaccination of solid organ transplant recipients admitted to the Sicilian solid organ transplant Reference Center IRCCS-ISMETT in Palermo during 2014–2015 influenza season. Thirty one (37.8%) out of 82 solid organ transplant recipients were vaccinated against influenza. The main reason for vaccination refusal was fear of adverse reaction (n = 16, 31.4%), impaired health status (n = 14, 27.4%) and low vaccine efficacy (n = 10, 19.6%). Vaccinated solid organ transplant recipients compare with unvaccinated had smaller hospital admissions for infectious respiratory diseases (9.7% Vs 23.5%) during surveillance period. On multivariate analysis the factors positively associated with influenza vaccination were the advice of Reference Center physicians (OR 53.4, p < 0.001) and to perform vaccine against pneumococcus (OR 7.0, p = 0.016). This study showed that Reference Center physicians play a key role on vaccine communication and recommendation for patients at risk and it underlines the effectiveness of influenza vaccination in solid organ transplant recipients. However, it remains that, although physician advice resulted a strong determinant for vaccination, influenza vaccination coverage in this subset of population remains still unsatisfactory.

Targeting pediatric versus elderly populations for norovirus vaccines: a model-based analysis of mass vaccination options

BackgroundNoroviruses are the leading cause of acute gastroenteritis and foodborne diarrheal disease in the United States. Norovirus vaccine development has progressed in recent years, but critical questions remain regarding which age groups should be vaccinated to maximize population impact. MethodsWe developed a deterministic, age-structured compartmental model of norovirus transmission and immunity in the U.S. population. The model was fit to age-specific monthly U.S. hospitalizations between 1996 and 2007. We simulated mass immunization of both pediatric and elderly populations assuming realistic coverages of 90% and 65%, respectively. We considered two mechanism of vaccine action, resulting in lower vaccine efficacy (lVE) between 22% and 43% and higher VE (hVE) of 50%. ResultsPediatric vaccination was predicted to avert 33% (95% CI: 27%, 40%) and 60% (95% CI: 49%, 71%) of norovirus episodes among children under five years for lVE and hVE, respectively. Vaccinating the elderly averted 17% (95% CI: 12%, 20%) and 38% (95% CI: 34%, 42%) of cases in 65+ year olds for lVE and hVE, respectively. At a population level, pediatric vaccination was predicted to avert 18–21 times more cases and twice as many deaths per vaccinee compared to elderly vaccination. ConclusionsThe potential benefits are likely greater for a pediatric program, both via direct protection of vaccinated children and indirect protection of unvaccinated individuals, including adults and the elderly. These findings argue for a clinical development plan that will deliver a vaccine with a safety and efficacy profile suitable for use in children.

Measles Outbreak Due to Low Vaccine Efficacy and Coverage, Mewat, Haryana, India 2015

Measles Outbreak Due to Low Vaccine Efficacy and Coverage, Mewat, Haryana, India 2015

Effect of vaccination age on cost-effectiveness of human papillomavirus vaccination against cervical cancer in China.

BackgroundThe cost-effectiveness of human papillomavirus (HPV) vaccination in women pre-sexual debut has been demonstrated in many countries. This study aimed to estimate the cost-effectiveness of a 3-dose bivalent HPV vaccination at ages 12 to 55 year in both rural and urban settings in China.MethodsThe Markov cohort model simulated the natural history of HPV infection and included the effect of screening and HPV vaccination over the lifetime of a 100,000 female cohort. Transition probabilities and utilities were obtained from published literature. Cost data were estimated by Delphi panel using healthcare payers’ perspective. Vaccine cost was assumed Hong Kong listed price. Vaccine efficacy (VE) was based on the PATRICIA trial data assuming VE irrespective of HPV type at all ages on incident HPV. Costs and outcomes were discounted at 3 %. Cervical cancer cases and incremental cost-effectiveness ratio (ICER) for vaccination and screening compared with screening alone were estimated for each vaccination age. Reduced VE in women post-sexual debut were investigated in scenario analyses.ResultsWith 70 % vaccination coverage, a reduction of cancer cases varying from 585 to 33 in rural and 691 to 32 in urban were estimated at ages 12 to 55, respectively. The discounted ICERs of vaccination at any age under 23 years in rural and any age under 25 years in urban were lower than the current threshold. Scenario analyses with lower VE post-sexual debut confirmed the results with age 20 in rural and 21 in urban had consistent lower ICERs. The more ‘catch-up’ cohorts vaccinated at the start of a program, the more cancer lesions are avoided in the long-term.ConclusionsVaccination at any age under 23 years old in rural and any age under 25 years old in urban were cost-effective. Catch-up to the age of 25 years in rural and urban could still be cost-effective.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2207-3) contains supplementary material, which is available to authorized users.

Economic value of mitigating Actinobacillus pleuropneumoniae infections in pig fattening herds

Actinobacillus pleuropneumoniae infections (APP) can cause severe economic losses in pig production. Swine producers can prevent the disease from occurring and spreading. However, to be profitable for the producer, the anticipated benefits of a mitigation policy should exceed its cost.In this study, a dynamic programming model and multivariate normal approximation of general stochastic epidemic model (SIR) was developed, and policies for managing fattening pigs under the risk of APP infection were evaluated. The following disease mitigation options were considered: 1) cleaning including washing, drying and disinfection procedures (for efficient and inefficient cleaning), 2) cleaning and vaccination (with high, medium and low efficacy of vaccine), and 3) cleaning and medication (antibiotics use). The results were calculated for five different levels of APP prevalence, where the disease can occur at ten levels of severity.The economic value of mitigation policy depended on the prevalence and severity of disease as well as on the efficiency of the implemented mitigation protocol. The results suggest that inefficient cleaning caused substantial economic losses which can reach up to €20.2 per pig space unit per year.The cleaning and vaccination policy was economically superior over the policy of only cleaning when the prevalence of disease was high (>0.3), there was a severe clinical disease and the medium or high efficacy vaccine was available. Moreover, even when vaccination costs were decreased the vaccination policy was not economically favored in situations with low disease prevalence among herds (0.1 and 0.3).In cases of severe disease, the cleaning and medication policy resulted in higher economic benefits than cleaning or cleaning and vaccination with low and medium efficacy vaccine. With a high prevalence (>0.3) and substantial decrease in the average daily gain (ADG), the joint application of cleaning and medication was economically less favorable than cleaning combined with the use of the high efficacy vaccine. Therefore, the availability of high efficacy vaccine could benefit farms facing the severe forms of APP and help to reduce the use of antibiotics.To avoid substantial economic losses, pig producers should not ignore cleaning procedures, which due to low efficacy of available vaccines and concerns regarding excessive use of antibiotics and antibiotic resistance in animal production should be the primary policy to mitigate APP.

The impacts of simultaneous disease intervention decisions on epidemic outcomes

Mathematical models of the interplay between disease dynamics and human behavioural dynamics can improve our understanding of how diseases spread when individuals adapt their behaviour in response to an epidemic. Accounting for behavioural mechanisms that determine uptake of infectious disease interventions such as vaccination and non-pharmaceutical interventions (NPIs) can significantly alter predicted health outcomes in a population. However, most previous approaches that model interactions between human behaviour and disease dynamics have modelled behaviour of these two interventions separately. Here, we develop and analyze an agent based network model to gain insights into how behaviour toward both interventions interact adaptively with disease dynamics (and therefore, indirectly, with one another) during the course of a single epidemic where an SIRV infection spreads through a contact network. In the model, individuals decide to become vaccinated and/or practice NPIs based on perceived infection prevalence (locally or globally) and on what other individuals in the network are doing. We find that introducing adaptive NPI behaviour lowers vaccine uptake on account of behavioural feedbacks, and also decreases epidemic final size. When transmission rates are low, NPIs alone are as effective in reducing epidemic final size as NPIs and vaccination combined. Also, NPIs can compensate for delays in vaccine availability by hindering early disease spread, decreasing epidemic size significantly compared to the case where NPI behaviour does not adapt to mitigate early surges in infection prevalence. We also find that including adaptive NPI behaviour strongly mitigates the vaccine behavioural feedbacks that would otherwise result in higher vaccine uptake at lower vaccine efficacy as predicted by most previous models, and the same feedbacks cause epidemic final size to remain approximately constant across a broad range of values for vaccine efficacy. Finally, when individuals use local information about others’ behaviour and infection prevalence, instead of population-level information, infection is controlled more efficiently through ring vaccination, and this is reflected in the time evolution of pair correlations on the network. This model shows that accounting for both adaptive NPI behaviour and adaptive vaccinating behaviour regarding social effects and infection prevalence can result in qualitatively different predictions than if only one type of adaptive behaviour is modelled.

Molecular characterisation of wild-type G1P[8] and G3P[8] rotaviruses isolated in Vietnam 2008 during a vaccine trial.

Rotavirus vaccines work better in developed countries than in developing countries, leading to the question of whether the circulating strains are different in these two settings. In 2008, a clinical trial of the pentavalent rotavirus vaccine was performed in Nha Trang, Vietnam, in which the efficacy was reported to be 64%. Although samples were collected independently from the clinical trial, we examined faecal specimens from children hospitalised for rotavirus diarrhoea and found that G3P[8] and G1P[8] were co-dominant at the time of the clinical trial. The aim of this study was to explore whether they were divergent from the strains circulating in the developed countries where the vaccine efficacy is high. Two G3P[8] and two G1P[8] strains that were regarded as representatives based on their electropherotypes were selected for full-genome sequencing. The genotype constellation was G1/G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. All but the VP4 genes, one of which belonged to the emerging P[8]b genotype (OP354-like VP4), clustered into one or more lineages/alleles with the strains circulating in developed countries, with ≥97.5% nucleotide sequence identity. Additionally, 10 G1 and 12 G3 VP7 sequences as well as 31 VP4 sequences were determined. No amino acid differences were observed between the Vietnamese strains and strains in the developed countries that were likely to have affected the neutralisation specificity of their VP7 and VP4. In conclusion, apart from prevalent P[8]b VP4, virtually no differences were observed between the predominant strains circulating in Vietnam at the time of the clinical trial and the strains in the developed countries; hence, the lower vaccine efficacy was more likely to be due to factors other than strain divergence.