Effectiveness of the BSE interventions in Japan.

Using a stochastic simulation model, we estimated the effectiveness of the three BSE interventions (SRM removal, post-mortem testing and cohort culling) in Japan, in terms of the amount of bovine ID50 that would be prevented from entering the human food supply and the number of life years that would be saved from resulting vCJD cases. The average reduction of the BSE load on the human food supply under SRM removal was 97% over the period from 2002 to 2009. The average reduction of the BSE load under most-mortem testing was 83% over the period from 2002 to 2007. The risk reducing effect of the three interventions combined was 99%. The maximum number of life years saved by the three interventions combined was 40.84 in 2006.

Cost-effectiveness of potential infant vaccination against respiratory syncytial virus infection in The Netherlands.

INTRODUCTION: Respiratory syncytial virus (RSV) infection is one of the major causes of respiratory illness in infants, infecting virtually every child before the age of 2 years. Currently, several Phase 1 trials with RSV vaccines in infants are ongoing or have been completed. As yet, no efficacy estimates are available for these vaccine candidates. Nevertheless, cost-effectiveness estimates might be informative to enable preliminary positioning of an RSV vaccine. METHODS: A decision analysis model was developed in which a Dutch birth cohort was followed for 12 months. A number of potential vaccination strategies were reviewed such as vaccination at specific ages, a two- or three-dosing scheme and seasonal vaccination versus year-round vaccination. The impact of the assumptions made was explored in various sensitivity analyses, including probabilistic analysis. Outcome measures included the number of GP visits, hospitalizations and deaths, costs, quality-adjusted life years and incremental cost-effectiveness ratios (ICERs). RESULTS: Currently, without vaccination, an annual number of 28,738 of RSV-related GP visits, 1623 hospitalizations, and 4.5 deaths are estimated in children in the age of 0-1 year. The total annual cost to society of RSV in the non-vaccination scenario is €7.7 million (95%CI: 1.7-16.7) and the annual disease burden is estimated at 597 QALYs (95%CI: 133-1319). In case all infants would be offered a potentially safe and effective 3-dose RSV vaccination scheme at the age of 0, 1 and 3 months, the total annual net costs were estimated to increase to €21.2 million, but 544 hospitalizations and 1.5 deaths would be averted. The ICER was estimated at €34,142 (95%CI: € 21,652-€ 87,766) per QALY gained. A reduced dose schedule, seasonal vaccination, and consideration of out-of-pocket expenses all resulted in more favorable ICER values, whereas a reduced vaccine efficacy or a delay in the timing of vaccination resulted in less favorable ICERs. DISCUSSION: Our model used recently updated estimates on the burden of RSV disease in children and it included plausible utilities. However, due to the absence of clinical trial data, a number of crucial assumptions had to be made related to the characteristics of potential RSV vaccine. The outcomes of our modeling exercise show that vaccination of infants against RSV might be cost-effective. However, clinical trial data are warranted.

The price of the precautionary principle: cost-effectiveness of BSE intervention strategies in The Netherlands.

Since 1996, bovine spongiform encephalopathy (BSE) in cattle has been linked to a new variant of Creutzfeldt-Jakob disease (vCJD), a fatal brain disease in man. This paper assessed the cost-effectiveness of BSE control strategies instituted by the European Commission. In a Monte Carlo simulation model, a non-intervention baseline scenario was compared to three intervention strategies: removal of specified risk materials from slaughter animals, post-mortem testing for BSE and the culling of feed and age cohorts of BSE cases. The food risk in the baseline scenario ranged from 16.98 lost life years in 2002 to 2.69 lost life years in 2005. Removing specified risk materials removal practices, post-mortem testing and post-mortem testing plus cohort culling reduced this risk with 93%, 82.7% and 83.1%. The estimated cost-effectiveness of all BSE measures in The Netherlands ranged from 4.3 million euros per life year saved in 2002 to 17.7 million euros in 2005. It was discussed that the cost-effectiveness of BSE control strategies will further deviate from regular health economics thresholds as BSE prevalence and incidence declines.

Simulation modeling to evaluate the persistence of Mycobacterium avium subsp. paratuberculosis (MAP) on commercial dairy farms in the United States.

We developed a series of deterministic mathematical models of Mycobacterium avium subsp. paratuberculosis (MAP) transmission on commercial US dairies. Our models build upon and modify models and assumptions in previous work to better reflect the pathobiology of the disease. Parameter values were obtained from literature for animal turnover in US dairy herds and rates of transition between disease states. The models developed were used to test three hypotheses. (1) Infectious transmission following intervention is relatively insensitive to the presence of high-shedding animals. (2) Vertical and pseudo-vertical transmission increases prevalence of disease but is insufficient to explain persistence following intervention. (3) Transiently shedding young animals might aid persistence. Our simulations indicated that multiple levels of contagiousness among infected adult animals in combination with vertical transmission and MAP shedding in infected young animals explained the maintenance of low-prevalence infections in herds. High relative contagiousness of high-shedding adult animals resulted in these animals serving as the predominant contributor to transmission. This caused elimination of infection in herds using the test-and-cull intervention tested in these simulations. Addition of vertical transmission caused persistence of infection in a moderately complicated model. In the most complex model that allowed age-based contacts, calf-to-calf transmission was required for persistence.

Transmission parameters of Mycobacterium avium subspecies paratuberculosis infections in a dairy herd going through a control program.

A Johne's disease control program, including stringent management practices and a test-and-cull program (whole-herd fecal-samples taken twice a year), was implemented on a medium-sized Pennsylvania dairy farm that was suffering losses from clinical Johne's disease. The data that emerged from the control program, combined with birthdates, culling dates, lactation information and pedigrees, yielded an extensive longitudinal dataset. The dataset was processed through SAS 9.1 for statistical analysis; herd-level disease dynamics and dam-to-daughter transmission parameters were calculated. After the implementation of the program in 1984, prevalence dropped dramatically from 60% to less than 20% in 1989. After an apparent prevalence peak (25%) in 1991 due to improved test sensitivity, prevalence maintained a plateau of 10% from 1996 to 2000. After the implementation of the program, 9.5% of the offspring from test-negative dams and 26.8% of the offspring from known-infected dams became infected with Mycobacterium avium subspecies paratuberculosis (Map) (chi(2)=14.7; p=0.0001). Calves born shortly following the calving of an infected dam and calves growing up with a future high shedder were more likely to be infected compared to calves without this risk profile. It was concluded that, after the implementation of the control program, the most important causes of infections of susceptible calves were their own dams or infected animals which had calved recently.