Pre-emptive Vaccination Research Articles

Rabies-induced behavioural changes are key to rabies persistence in dog populations: Investigation using a network-based model.

Canine rabies was endemic pre-urbanisation, yet little is known about how it persists in small populations of dogs typically seen in rural and remote regions. By simulating rabies outbreaks in such populations (50–90 dogs) using a network-based model, our objective was to determine if rabies-induced behavioural changes influence disease persistence. Behavioural changes–increased bite frequency and increased number or duration of contacts (disease-induced roaming or paralysis, respectively)–were found to be essential for disease propagation. Spread occurred in approximately 50% of model simulations and in these, very low case rates (2.0–2.6 cases/month) over long durations (95% range 20–473 days) were observed. Consequently, disease detection is a challenge, risking human infection and spread to other communities via dog movements. Even with 70% pre-emptive vaccination, spread occurred in >30% of model simulations (in these, median case rate was 1.5/month with 95% range of 15–275 days duration). We conclude that the social disruption caused by rabies-induced behavioural change is the key to explaining how rabies persists in small populations of dogs. Results suggest that vaccination of substantially greater than the recommended 70% of dog populations is required to prevent rabies emergence in currently free rural areas.

Targeted pre-emptive rabies vaccination strategies in a susceptible domestic dog population with heterogeneous roaming patterns

Australia is free of canine rabies, however northern regions – such as the Northern Peninsula Area (NPA), Queensland – are at risk of an incursion from nearby rabies-infected Indonesian islands. Early detection and reactive vaccination is the current Australian policy to eradicate an incursion. Early detection in this region is challenging, so pre-emptive vaccination might be an effective strategy. The NPA dog population also has a heterogenous contact structure, with three roaming categories previously characterised, which could be exploited in targeted pre-emptive vaccination strategies for more efficient use of limited resources. To evaluate the effectiveness of a pre-emptive vaccination program, an agent-based rabies spread simulation model was used to simulate outbreaks with a range of pre-emptive vaccination coverages. Increasing proportions (10% increments) of the dog population randomly vaccinated were modelled, and at the most efficient random vaccination coverage we then explored 10 pre-emptive vaccination strategies targeting different dog roaming categories (whilst maintaining the same overall population level vaccination coverage). All pre-emptive vaccination strategies were simulated 2000 times without and with a 70% random reactive vaccination strategy, following rabies detection. All random pre-emptive vaccination coverages reduced outbreak size and duration compared to no pre-emptive vaccination. A 40% random coverage was most efficient. Targeted strategies that pre-emptively vaccinated proportionally more roaming dogs were more effective than a random 40% vaccination coverage and strategies that targeted non-roaming dogs. The pre-emptive vaccination strategies that targeted non-roaming dogs produced significantly larger and longer outbreaks. These results suggest that pre-emptive vaccination can reduce potential rabies outbreaks in this region and that such a strategy should not just focus on easily accessible dogs that do not roam often or at all. A cost-benefit analysis is required to determine whether the implementation of such pre-emptive vaccination strategies is also cost-effective, which is essential in the resource-poor communities of this region.

A game theoretic approach to discuss the positive secondary effect of vaccination scheme in an infinite and well-mixed population

Abstract Pre-emptive vaccination policy used in controlling the rapid spreading of infectious diseases is considered as one of the most challenging issues imposed to mankind, causing enormous death tolls over the years. This paper dedicatedly studies the dilemma effect coming from the failure of getting perfect immunity to those individuals who committed vaccination earlier. Therefore, we propose a new theoretical model that slows down the infection spreading and also facilitates quicker recovery time than what the previous model does even if a vaccinator fails to obtain perfect immunity. We name this effect as the “positive secondary effect” of vaccination as it gives a second chance to the vaccinators which in return subdues the rapid spreading that helps in producing better social average payoff as well as keeping the final epidemic size smaller. Moreover, to address the positive secondary effect more precisely, we introduce two different parameters; namely, relaxation parameter (η) and foster parameter (δ) in two different directions to quantify the individual effects resulting from each of the parameter space as well as their superposition effect. An in-depth discussion focuses on the influential role played by our proposed model via discounting and faster recovery effects while a second chance is given to the vaccinators. In addition, we also examine the situation when discounting effect brought by η outperforms very much than its faster recovery controlled by δ as well as the superposition effects. Unlike all previous studies dealing with vaccination game, we pay much attention to investigating the secondary effect of imperfect vaccination policy. Our proposed theoretical scheme completely reproduces the decision-making process of choosing an imperfect provision based on evolutionary game theory entailed with the widely used SIR (Susceptible–Infected–Recovered) epidemic model. Without considering any spatial structure and perfect vaccination policy, our model presumes the population being infinite and well-mixed to represent the infection spreading dynamics mathematically. This study is conducted throughout using the so-called theoretical approach. Besides that, three different updating rules based on evolutionary game theory have also been considered to investigate all possible situations. Later on, we draw 2D full phase diagrams showing the final epidemic size, vaccination coverage, and average social payoff quantitatively. Finally, our theoretical result is compared with the counterpart result obtained from the multi-agent simulation (MAS) approach and a good agreement is found, hence the appropriateness of the proposed model is fully justified.

Confronting Public Health Imperialism: A Transnational Feminist Analysis of Critical Nurse Responses to the National Smallpox Vaccination Program of 2002

Confronting Public Health ImperialismA Transnational Feminist Analysis of Critical Nurse Responses to the National Smallpox Vaccination Program of 2002 Gwen D'Arcangelis (bio) small acts of resistance: gender and imperialism The juggernaut of US empire known as the "War on Terror" is by now a familiar, ubiquitous part of the twenty-first century. Less familiar to most is one of its early missteps, namely, the National Smallpox Vaccination Program (NSVP), a biodefense program that the Bush Administration devised to protect the US from a bioterror attack. From late 2002 to mid-2003, the federal government, arguing that a potential attack might occur from the likes of Al Qaeda or Iraq, attempted to recruit the health care field into a preemptive vaccination program against smallpox. Nurses were among the prominent occupational categories targeted, and more important, among the leading groups who challenged the program on the grounds of its health risks and role in the Iraq war. In this article I chronicle the multilayered intervention that US nurses made in the NSVP, specifically their reworking of hegemonic scientific and national security discourses. Nurse intervention into the NSVP is significant for two reasons. First, nurses reclaimed their centrality as decision makers in the NSVP, a prominent public health campaign that, as I show, exploited their labor and marginalized their medical expertise. Feminist scholars have analyzed nursing as a feminized labor domain long beset with the historical character of "women's work"—for example, low wages and devalued expertise.1 I demonstrate that nurses' defiance of the NSVP contributes significantly to a legacy of resistance to these conditions. Second, nurses challenged the NSVP based on its connection to the US program of aggression in Iraq and the War on Terror during a period of extreme "patriotism," when it was difficult to wage criticism of the US national security apparatus. Remarkably, US nurses linked their struggles for better safety and protections to a broader critique of US imperialism. In doing so, I argue, they enacted a model of transnational feminist praxis [End Page 95] wherein women in global north and imperial nations hold their governments accountable for perpetrating oppressive practices of imperialism and other forms of structural violence against less powerful nations in the global south. Transnational feminist theory builds on the intersectional analysis forwarded by feminist theorists such as Kimberle Crenshaw2 and Patricia Hill Collins,3 who analyze women's struggles through a gendered lens that considers how race, class, nation, and other socio-structural positions determine gender relations and social power. Transnational feminist theorists focus on the intersection between gender and nation, noting that women across the globe are not only connected by their commonalities but also severely divided, particularly along the axis of colonialism and imperialism. They have noted that many feminist movements in imperial countries have been insufficiently critical of their government's expansionist foreign policy and imperialist practices globally, at times even joining forces to further them. Transnational feminist scholars have criticized the US-based Feminist Majority Foundation, for instance, for aligning itself with the US government's war on Afghanistan and its paternalistic rescue mission to save Afghani women, in the process marginalizing Afghani feminists' work and leadership.4 Transnational feminist theorists espouse that women in imperial nations should attend to their complicity in the actions of their governments. In the context of the most recent bouts of US imperialism targeting Afghanistan and Iraq, transnational feminist scholars such as Chandra Mohanty have challenged global north feminists to be self-reflexive about their political praxis (politically informed theory and action): What role have US feminists who supported the Bush administration's war in the name of "rescuing" Afghan and Iraqi women played in [the] narrative of empire and imperialism? This is one of the questions we need to pose to address the politics of complicity and dissent within contemporary feminist projects.5 In addition to calling for feminists in imperial and global north nations to reexamine their role in US imperial violence, she also highlights US imperialism as a key site for transnational feminist engagement: The militarized US State and its imperial projects are thus a crucial site of feminist struggle both in terms of the violence...

683. Cost Calculator for Mass Vaccination Response to a US College Campus Outbreak of Serogroup B Meningococcal Disease

BackgroundUS college students are at increased risk for serogroup B meningococcal disease (MenB). MenB caused ~57% of meningococcal disease cases among 16- to 23-year-olds in 2016, and was responsible for 10 US college outbreaks from 2011−2017 involving 41 cases and an at-risk population of ~182,000 enrolled undergraduates. Outbreaks cause disruptive anxiety among university communities and implementing a mass vaccination response imposes an often unforeseen financial burden. This study aimed to enumerate costs incurred during a points-of-dispensing, mass vaccination response to a US campus MenB outbreak.MethodsThe 2015 MenB outbreak at Providence College was used as a case study to develop an Excel-based (Microsoft, Redmond, WA) cost calculator to capture costs and resources associated with a MenB outbreak response. The calculator has user-modifiable inputs related to the vaccine-eligible population, accounts for each vaccination event and vaccine dose (Figure 1), and estimates direct costs (2016 USD) during 18 months post-outbreak. Potential/expected costs computed (assuming 100% vaccine coverage) were compared with estimated actual costs incurred during the outbreak, using a micro-costing approach.ResultsThe estimated total cost for full vaccination of 4,795 eligible individuals was $1,798,399 ($375.06/person); based on actual vaccinations received, the cost calculator computed $1,350,963 in aggregate direct costs ($636.05/person fully vaccinated) (Table 1). In both analyses, medical supplies were the majority of costs (88–89%), followed by labor resources (7–9%).ConclusionThis cost calculator quantifies the direct cost of a mass vaccination response to one campus MenB outbreak. Although the cost estimates herein are higher than previously reported, the calculator does not account for follow-up costs or productivity losses and therefore underestimates the true economic burden of a campus MenB outbreak. This outbreak response cost calculator can be used to aid in response planning and highlights the need to shift the public health response from outbreak control to prevention by proactive, pre-emptive vaccination using available licensed meningococcal vaccines.Figure 1.Timeline of vaccination clinicsDisclosures E. M. La, RTI Health Solutions (RTI-HS): Employee and RTI-HS is an independent scientific research organization which was retained pursuant to a contract with Pfizer to conduct the research services which are the subject of this presentation/abstract., Salary and The RTI-HS employees who worked on this project did not receive compensation from Pfizer or any other organization, other than RTI-HS salaries.. S. E. Talbird, RTI Health Solutions (RTI-HS): Employee and RTI-HS is an independent scientific research organization which was retained pursuant to a contract with Pfizer to conduct the research services which are the subject of this presentation/abstract., Salary and The RTI-HS employees who worked on this project did not receive compensation from Pfizer or any other organization, other than RTI-HS salaries.. J. Fain, Pfizer Inc.: Employee at time of Study and Employee, Salary. L. Huang, Pfizer: Employee and Shareholder, Salary and Stocks. A. Srivastava, Pfizer: Employee and Shareholder, Salary and Stocks.

Reactive and pre-emptive vaccination strategies to control hepatitis E infection in emergency and refugee settings: A modelling study.

BackgroundHepatitis E Virus (HEV) is the leading cause of acute viral hepatitis globally. Symptomatic infection is associated with case fatality rates of ~20% in pregnant women and it is estimated to account for ~10,000 annual pregnancy-related deaths in southern Asia alone. Recently, large and well-documented outbreaks with high mortality have occurred in displaced population camps in Sudan, Uganda and South Sudan. However, the epidemiology of HEV is poorly defined, and the value of different immunisation strategies in outbreak settings uncertain. We aimed to estimate the critical epidemiological parameters for HEV and to evaluate the potential impact of both reactive vaccination (initiated in response to an epidemic) and pre-emptive vaccination.MethodsWe analysed data from one of the world's largest recorded HEV epidemics, which occurred in internally-displaced persons camps in Uganda (2007–2009), using transmission dynamic models to estimate epidemiological parameters and assess the potential impact of reactive and pre-emptive vaccination strategies.ResultsUnder baseline assumptions we estimated the basic reproduction number of HEV in three separate camps to range from 3.7 (95% Credible Interval [CrI] 2.8, 5.1) to 8.5 (5.3, 11.4). Mean latent and infectious periods were estimated to be 34 (95% CrI 28, 39) and 40 (95% CrI 23, 71) days respectively.Assuming 90% vaccine coverage, reactive two-dose vaccination of those aged 16–65 years excluding pregnant women (for whom vaccine is not licensed), if initiated after 50 reported cases, led to mean camp-specific reductions in mortality of 10 to 29%. Pre-emptive vaccination with two doses reduced mortality by 35 to 65%. Both strategies were more effective if coverage was extended to groups for whom the vaccine is not currently licensed. For example, two dose pre-emptive vaccination, if extended to include pregnant women, led to mean reductions in mortality of 66 to 82%.ConclusionsHEV has a high transmission potential in displaced population settings. Substantial reductions in mortality through vaccination are expected, even if used reactively. There is potential for greater impact if vaccine safety and effectiveness can be established in pregnant women.

Responding to yellow fever outbreaks in West and Central Africa: Rapid prioritization assessment for the pre-emptive vaccination campaigns

Introduction Recent yellow fever (YF) outbreaks in Africa, such as 2016 in Angola, or 2017 in Nigeria, have demonstrated the ongoing threat of large-scale urban YF outbreaks. Moreover, outbreaks of other mosquito-borne diseases (Zika, chikungunya) have increased awareness of the potential for rapid, international spread of arboviruses. Swift outbreak response, for YF primarily in the form of vaccination, is therefore essential to prevent local and international spread. However, limited global stockpiles means that the prioritization of geographic areas for pre-emptive vaccination campaigns is required (i.e. vaccination campaigns targeting areas that are at risk of disease introduction and spread but as yet unaffected). Conducting a rapid prioritization assessment based on the risk of disease spread is thus highly valuable to inform decisions on vaccination activities in a context of emergency. Objective To develop a method for rapid risk assessment of YF spread to prioritize sub-national administrative units (hereafter called province) for pre-emptive campaigns. Specific requirements for this method are: –speed of implementation in the context of emergency response; –transparent methodology to allow discussions with and feedback from decision-makers. Method We developed a heuristic method to quantify the risk of YF spread by integrating multiple data streams: population sizes, estimates of existing vaccine-induced population-level immunity, recent incidence of yellow fever cases in the province and travel flows between provinces. The resulting risk score primarily reflects the expected absolute number of yellow cases in the respective province, accounting for local cases and the risk of case importation. Based on their risk score, provinces are ranked according to priority for vaccination and target population sizes are estimated. This baseline, quick-to-compute, risk assessment can be refined by integrating additional elements. For example, the presence and population size of large urban centres at the province level may be relevant to characterize the risk of urban outbreaks, and of international spread in the case of highly connected urban centres. Similarly, independent estimates of the local transmission potential of the disease produced by a mathematical model can be combined into this risk metric. Results This heuristic method has been used in collaboration with the World Health Organization in the context of urgent response to yellow fever outbreaks that affected Angola and the Democratic Republic of Congo (DRC) in 2016 and Nigeria in 2017. Results were provided in a form that allowed decision-makers to easily and interactively adjust the relative weights of different factors and visualize the effect on the results. Moreover, the transparency of the method allowed decision-makers to provide feedback and to request the integration of additional elements considered as relevant for outbreak control (for instance: trans-border movements in Angola-DRC). This risk assessment contributed to inform decision for mass vaccination campaigns conducted in the DRC in 2017 and for campaigns (still under consideration) in Nigeria in 2018. Conclusion By integrating different, mostly publicly available, data streams, we developed a risk assessment method that can be quickly implemented in the context of yellow fever outbreak response. The transparency and flexibility of the method enhanced interactions with decision-makers to refine estimates.

Cost-of-illness of cholera to households and health facilities in rural Malawi.

Cholera remains an important public health problem in many low- and middle-income countries. Vaccination has been recommended as a possible intervention for the prevention and control of cholera. Evidence, especially data on disease burden, cost-of-illness, delivery costs and cost-effectiveness to support a wider use of vaccine is still weak. This study aims at estimating the cost-of-illness of cholera to households and health facilities in Machinga and Zomba Districts, Malawi. A cross-sectional study using retrospectively collected cost data was undertaken in this investigation. One hundred patients were purposefully selected for the assessment of the household cost-of-illness and four cholera treatment centres and one health facility were selected for the assessment conducted in health facilities. Data collected for the assessment in households included direct and indirect costs borne by cholera patients and their families while only direct costs were considered for the assessment conducted in health facilities. Whenever possible, descriptive and regression analysis were used to assess difference in mean costs between groups of patients. The average costs to patients’ households and health facilities for treating an episode of cholera amounted to US$65.6 and US$59.7 in 2016 for households and health facilities, respectively equivalent to international dollars (I$) 249.9 and 227.5 the same year. Costs incurred in treating a cholera episode were proportional to duration of hospital stay. Moreover, 52% of households used coping strategies to compensate for direct and indirect costs imposed by the disease. Both households and health facilities could avert significant treatment expenditures through a broader use of pre-emptive cholera vaccination. These findings have direct policy implications regarding priority investments for the prevention and control of cholera.

Reactive and pre-emptive vaccination strategies to control hepatitis E infection in emergency and refugee settings: a modelling study

This abstract corresponds with the following slides: https://f1000research.com/slides/6-691, presented at Medecins Sans Frontieres UK Scientific Days: Medical Research 2017. To watch the presentation click here: https://f1000research.com/videos/6-831. This abstract is part of an F1000Research gateway that includes posters, slides and videos from the MSF Scientific Day: Medical Research 2017. To see more please visit: https://f1000research.com/gateways/MSF/scidays

Knowledge, Attitudes, and Practices regarding Diarrhea and Cholera following an Oral Cholera Vaccination Campaign in the Solomon Islands

BackgroundIn response to a 2011 cholera outbreak in Papua New Guinea, the Government of the Solomon Islands initiated a cholera prevention program which included cholera disease prevention and treatment messaging, community meetings, and a pre-emptive cholera vaccination campaign targeting 11,000 children aged 1–15 years in selected communities in Choiseul and Western Provinces.Methodology and Principal FindingsWe conducted a post-vaccination campaign, household-level survey about knowledge, attitudes, and practices regarding diarrhea and cholera in areas targeted and not targeted for cholera vaccination. Respondents in vaccinated areas were more likely to have received cholera education in the previous 6 months (33% v. 9%; p = 0.04), to know signs and symptoms (64% vs. 22%; p = 0.02) and treatment (96% vs. 50%; p = 0.02) of cholera, and to be aware of cholera vaccine (48% vs. 14%; p = 0.02). There were no differences in water, sanitation, and hygiene practices.ConclusionsThis pre-emptive OCV campaign in a cholera-naïve community provided a unique opportunity to assess household-level knowledge, attitudes, and practices regarding diarrhea, cholera, and water, sanitation, and hygiene (WASH). Our findings suggest that education provided during the vaccination campaign may have reinforced earlier mass messaging about cholera and diarrheal disease in vaccinated communities.

Clinical Review of Shanchol™ (a WHO pre-qualified oral cholera vaccine)

Background: Cholera caused by Vibrio cholerae of the O1 or O139 serogroup is an important cause of severe dehydrating diarrhea in adults and children. It continues to be a major global health problem. The WHO estimates that 3-5 million cases and 100,000–130,000 deaths occur per year globally, predominantly in Asia and Africa. The WHO recommends that in cholera-endemic countries, vaccination should be used as an additional tool to control cholera along with longer term interventions of improving water and sanitation. It recommends pre-emptive vaccination to help prevent potential outbreaks or the spread of current outbreaks. Shanchol™ is a ready-to-use killed bivalent (O1 and O139) whole-cell oral cholera vaccine administered as 2 doses 14 days apart in individuals aged 1 year and above. There is no need for buffer or water for its administration. It is currently licensed in India and 17 other countries in Asia, Africa and Latin America. It is prequalified for international use by the WHO. The vaccine is the basis for the WHO stockpile which is used to help control cholera epidemics. Methods & Materials: Clinical analysis of safety, immunogenicity and efficacy studies of Shanchol™ Results: Overall, ∼66,000 doses have been administered to subjects during the clinical development of the vaccine. Shanchol™ was observed to provide sustained protective efficacy level of 65% for at least 5 years in a clinical trial conducted in over 69,000 subjects in India. The herd effect conferred by Shanchol™ was evident with minimum vaccine coverage of 38% and was sustained for at least 3 years. Safety and immunogenicity clinical trials conducted in India, Bangladesh, Ethiopia, Philippines and Haiti showed that the vaccine is safe and provides good immune responses in different endemic populations. Results from a clinical study showed that flexible dosing schedule of Shanchol™ as 2 doses 14 to 28 days apart is possible. A modeling study observed that single-dose vaccination may prevent more deaths during outbreaks than 2-dose vaccination. Shanchol™ was also observed to be highly effective in mass vaccination campaigns in Guinea, Haiti, Odisha (India) and Bangladesh. Conclusion: Shanchol™ vaccine is safe and effective for control of cholera in endemic countries

The Impact of Population, Contact, and Spatial Heterogeneity on Epidemic Model Predictions.

Our objective was to evaluate the effect that complexity in the form of different levels of spatial, population, and contact heterogeneity has in the predictions of a mechanistic epidemic model. A model that simulates the spatiotemporal spread of infectious diseases between animal populations was developed. Sixteen scenarios of foot-and-mouth disease infection in cattle were analyzed, involving combinations of the following factors: multiple production-types (PT) with heterogeneous contact and population structure versus single PT, random versus actual spatial distribution of population units, high versus low infectivity, and no vaccination versus preemptive vaccination. The epidemic size and duration was larger for scenarios with multiple PT versus single PT. Ignoring the actual unit locations did not affect the epidemic size in scenarios with multiple PT/high infectivity, but resulted in smaller epidemic sizes in scenarios using multiple PT/low infectivity. In conclusion, when modeling fast-spreading epidemics, knowing the actual locations of population units may not be as relevant as collecting information on population and contact heterogeneity. In contrast, both population and spatial heterogeneity might be important to model slower spreading epidemic diseases. Our findings can be used to inform data collection and modeling efforts to inform health policy and planning.

Game theory of pre-emptive vaccination before bioterrorism or accidental release of smallpox.

Smallpox was eradicated in the 1970s, but new outbreaks could be seeded by bioterrorism or accidental release. Substantial vaccine-induced morbidity and mortality make pre-emptive mass vaccination controversial, and if vaccination is voluntary, then there is a conflict between self- and group interests. This conflict can be framed as a tragedy of the commons, in which herd immunity plays the role of the commons, and free-riding (i.e. not vaccinating pre-emptively) is analogous to exploiting the commons. This game has been analysed previously for a particular post-outbreak vaccination scenario. We consider several post-outbreak vaccination scenarios and compare the expected increase in mortality that results from voluntary versus imposed vaccination. Below a threshold level of post-outbreak vaccination effort, expected mortality is independent of the level of response effort. A lag between an outbreak starting and a response being initiated increases the post-outbreak vaccination effort necessary to reduce mortality. For some post-outbreak vaccination scenarios, even modest response lags make it impractical to reduce mortality by increasing post-outbreak vaccination effort. In such situations, if decreasing the response lag is impossible, the only practical way to reduce mortality is to make the vaccine safer (greater post-outbreak vaccination effort leads only to fewer people vaccinating pre-emptively).

MICROECOLOGY OF NASOPHARYNGEAL MUCOSAL MEMBRANES AND ESTIMATION OF FACTORS OF MUCOSAL AND LYMPHOCYTIC IMMUNITY IN RECRUITS DURING THE FORMATION OF ORGANIZED TEAM

Contamination of nasopharyngeal mucosa by opportunistic and pathogenic bacteria in practically healthy people during the formation of the close group has been accompanied by a dysfunction of mucosal immunity, imbalanceof cytokine profile, insolvency of antioxidant system, increasing endointoxication. Adequate changes of serum immunoglobulins level in patients with nasopharyngeal dysbiosis allow to conclude of usefulness of the pre-emptive vaccination and using drugs with immunomodulatory effect which reliably satisfy body’s need for antioxidants.

Changing patterns of human anthrax in Azerbaijan during the post-Soviet and preemptive livestock vaccination eras.

We assessed spatial and temporal changes in the occurrence of human anthrax in Azerbaijan during 1984 through 2010. Data on livestock outbreaks, vaccination efforts, and human anthrax incidence during Soviet governance, post-Soviet governance, preemptive livestock vaccination were analyzed. To evaluate changes in the spatio-temporal distribution of anthrax, we used a combination of spatial analysis, cluster detection, and weighted least squares segmented regression. Results indicated an annual percent change in incidence of +11.95% from 1984 to 1995 followed by declining rate of −35.24% after the initiation of livestock vaccination in 1996. Our findings also revealed geographic variation in the spatial distribution of reporting; cases were primarily concentrated in the west early in the study period and shifted eastward as time progressed. Over twenty years after the dissolution of the Soviet Union, the distribution of human anthrax in Azerbaijan has undergone marked changes. Despite decreases in the incidence of human anthrax, continued control measures in livestock are needed to mitigate its occurrence. The shifting patterns of human anthrax highlight the need for an integrated “One Health” approach that takes into account the changing geographic distribution of the disease.

A model-based economic analysis of pre-pandemic influenza vaccination cost-effectiveness.

BackgroundA vaccine matched to a newly emerged pandemic influenza virus would require a production time of at least 6 months with current proven techniques, and so could only be used reactively after the peak of the pandemic. A pre-pandemic vaccine, although probably having lower efficacy, could be produced and used pre-emptively. While several previous studies have investigated the cost effectiveness of pre-emptive vaccination strategies, they have not been directly compared to realistic reactive vaccination strategies.MethodsAn individual-based simulation model of ~30,000 people was used to examine a pre-emptive vaccination strategy, assuming vaccination conducted prior to a pandemic using a low-efficacy vaccine. A reactive vaccination strategy, assuming a 6-month delay between pandemic emergence and availability of a high-efficacy vaccine, was also modelled. Social distancing and antiviral interventions were examined in combination with these alternative vaccination strategies. Moderate and severe pandemics were examined, based on estimates of transmissibility and clinical severity of the 1957 and 1918 pandemics respectively, and the cost effectiveness of each strategy was evaluated.ResultsProvided that a pre-pandemic vaccine achieved at least 30% efficacy, pre-emptive vaccination strategies were found to be more cost effective when compared to reactive vaccination strategies. Reactive vaccination coupled with sustained social distancing and antiviral interventions was found to be as effective at saving lives as pre-emptive vaccination coupled with limited duration social distancing and antiviral use, with both strategies saving approximately 420 life-years per 10,000 population for a moderate pandemic with a basic reproduction number of 1.9 and case fatality rate of 0.25%. Reactive vaccination was however more costly due to larger productivity losses incurred by sustained social distancing, costing $8 million per 10,000 population ($19,074/LYS) versus $6.8 million per 10,000 population ($15,897/LYS) for a pre-emptive vaccination strategy. Similar trends were observed for severe pandemics.ConclusionsCompared to reactive vaccination, pre-emptive strategies would be more effective and more cost effective, conditional on the pre-pandemic vaccine being able to achieve a certain level of coverage and efficacy. Reactive vaccination strategies exist which are as effective at mortality reduction as pre-emptive strategies, though they are less cost effective.

How do resources influence control measures during a simulated outbreak of foot and mouth disease in Australia?

An outbreak of foot and mouth disease (FMD) could seriously impact Australia's livestock sector and economy. As an FMD-free country, an outbreak would trigger a major disease control and eradication program that would include the culling of infected and at risk animals (‘stamping out’), movement restrictions and zoo-sanitary measures. Additional control measures may also include pre-emptive culling or vaccination. However, it is unclear what disease strategy would be most effective under Australian conditions and different resource levels. Using a stochastic simulation model that describes FMD transmission between farms in a livestock dense region of Australia, our results suggest that using current estimates of human resource capacity for surveillance, infected premises operations and vaccination, outbreaks were effectively controlled under a stamping out strategy. However, under more constrained resource allocations, ring vaccination was more likely to achieve eradication faster than stamping out or pre-emptive culling strategies.

Abstract A11: Insulin-like growth factor vaccine for the global prevention of adult cancers

Abstract The purpose of this study is to develop a single vaccine that will prevent a variety of different cancers. It functions by reducing the supply of insulin-like growth factor (IGF) required for carcinogenesis. A safe, widely applicable preemptive treatment can greatly curtail cancer deaths. Primary prevention precludes the confounding problems associated with advanced cancer such as its resistance to treatment, its eventual recurrence and the progression to metastatic disease. This novel prevention strategy is based on studies of a small population of individuals in Ecuador who are cancer free their entire lifetime due to genetically low IGF levels. In contrast, 14% of their IGF-replete relatives succumbed to 20 different types of malignancy. That compelling human example of the benefit of reduced IGF activity suggests that the initiation or early progression of many cancers requires IGF. Thus, the objective is to develop protective vaccines to neutralize the multiple activities of IGF that promote oncogenesis. The ultimate goal is to vaccinate at risk adults and achieve the same protection from cancer experienced by the IGF-deficient Ecuadorians. The concept is predicated on the hypothesis that a lingering high level of IGF stimulation is superfluous after adolescence and, in later years, becomes detrimental to health. There are strong survival benefits for its simultaneous mitogenic, hypertrophic and antiapoptotic activities to operate during growth and development. Alas, there is no evolutionary pressure to develop a post-reproductive IGF shutoff mechanism. So, as science and medicine steadily extend the human lifespan, we find ourselves in the dilemma of having to accommodate a persistent pro-cancer hormone with little or no other purpose. This hypothesis fits with the age dependent increase of cancer incidence. Conventional and cutting-edge, nanofiber-based epitope vaccines have been produced to test this idea. They are designed to actively induce antibodies that either neutralize IGF directly or block a key enzyme that regulates IGF bioavailability. The continuous presence of such inhibitory antibodies would keep IGF activity at a constantly low level and thereby preemptively block the development of incipient cancers later in life. Antisera from mice immunized with those vaccines contained epitope-specific IgG antibodies that were reactive with recombinant IGF in ELISA studies. An ultrafiltration method was also used to demonstrate specific binding of recombinant 125I-IGF after incubation with undiluted antiserum versus non-immune control sera (conditions that mimic in vivo therapy). Exploratory tests indicated that the vaccine delayed the appearance of tumors in mice that develop sarcomas due to SV40 Tag expression. Safety is undeniably paramount for any new cancer prevention therapy and apprehension about targeting the ubiquitously expressed IGF is understandable. In terms of human health consequences however, the IGF-deficient Ecuadorians represent a worst-case scenario since they are severely depleted from birth onwards. Although very short due to their life-long IGF deficit, this cancer-free population is surprisingly healthy and long-lived (some >80 years old). Nevertheless, to further ensure safety the IGF-suppressive vaccines will be administered exclusively to fully grown and developed adults. Preemptive vaccination at 40-50 years old would be most effective since a majority of human malignancies occur beyond the age of 60 and because this postponement will circumvent impairment of normal growth or other juvenile functions. The prevention vaccines could be used; 1) for people with a genetic likelihood to develop familial cancer, 2) as an adjuvant following precancerous growth removal, 3) to inhibit relapse for patients in remission, and 4) as a general prophylactic to curtail sporadic, age-dependent cancers. Citation Format: Victor Raso. Insulin-like growth factor vaccine for the global prevention of adult cancers. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A11.

Economic Analysis of HPAI Control in the Netherlands II: Comparison of Control Strategies

A combined epidemiological-economic modelling approach was used to analyse strategies for highly pathogenic avian influenza (HPAI) control for the Netherlands. The modelling framework used was InterSpread Plus (ISP), a spatially based, stochastic and dynamic simulation model. A total of eight control strategies were analysed, including pre-emptive depopulation and vaccination strategies. The analysis was carried out for three different regions in the Netherlands: high-, medium- and low-density areas (HDA, MDA and LDA, respectively). The analysis included the veterinary impact (e.g. number of infected premises and duration), but was particularly focused on the impact on direct costs (DC) and direct consequential costs. The efficient set of control strategies for HDA and MDA included strategies based on either pre-emptive depopulation only or combined vaccination and pre-emptive depopulation: D2 (pre-emptive depopulation within a radius of 2 km), RV3 + D1 (ring vaccination within a radius of 3 km and additional pre-emptive depopulation within a radius of 1 km) and PV + D1 (preventive vaccination in non-affected HDAs and pre-emptive depopulation within a radius of 1 km in the affected HDA). Although control solely based on depopulation in most cases showed to be effective for LDA, pre-emptive depopulation showed to have an additional advantage in these areas, that is, prevention of 'virus jumps' to other areas. The pros and cons of the efficient control strategies were discussed, for example, public perception and risk of export restrictions. It was concluded that for the Netherlands control of HPAI preferably should be carried out using strategies including pre-emptive depopulation with or without vaccination. Particularly, the short- and long-term implications on export, that is, indirect consequential costs (ICC) and aftermath costs of these strategies, should be analysed further.

RNA Interference for Viral Infections

The treatment of viral infections has relied on pre-emptive vaccination or use of a limited range of anti-viral drugs. However, the majority of viruses have no available drugs and treatment is merely supportive. RNA interference (RNAi) offers the ability to directly and rapidly treat virus infections via the targeting of viral genes. Indeed, clinical trials have already been undertaken with promising results. Here we review the current state of the RNAi field for the treatment of viral infections such as HIV, human papillomavirus and HCV. We also review novel strategies including the concept of targeting self-genes to limit viral infection and activating the immune system for improved outcomes. Finally we examine innovative approaches being pursued at the Australian Infectious Diseases Research Centre including the use of high-throughput siRNA screens to identify new antiviral targets.