ObjectiveTo review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost–effectiveness and recommendations for use, particularly in high-risk settings.MethodsWe searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines.FindingsPre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability.ConclusionPre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities.

ProblemUrbanization, large dog populations and failed control efforts have contributed to continuing endemicity of dog-mediated rabies in KwaZulu-Natal province, South Africa.ApproachFrom 2007 to 2014 we used a OneHealth approach to rabies prevention, involving both the human and animal health sectors. We implemented mass vaccination campaigns for dogs to control canine rabies, and strategies to improve rabies awareness and access to postexposure prophylaxis for people exposed to rabies.Local settingA rabies-endemic region, KwaZulu-Natal is one of the smallest and most populous South African provinces (estimated population 10 900 000). Canine rabies has persisted since its introduction in 1976, causing an average of 9.2 human rabies cases per annum in KwaZulu-Natal from 1976 to 2007, when the project started.Relevant changesBetween 2007 and 2014, the numbers of dog vaccinations rose from 358 611 to 395 000 and human vaccines purchased increased form 100 046 to 156 996. Strategic dog vaccination successfully reduced rabies transmission within dog populations, reducing canine rabies cases from 473 in 2007 to 37 in 2014. Actions taken to reduce the incidence of canine rabies, increase public awareness of rabies and improve delivery of postexposure prophylaxis contributed to reaching zero human rabies cases in KwaZulu-Natal in 2014.Lessons learntStarting small and scaling up enabled us to build strategies that fitted various local settings and to successfully apply a OneHealth approach. Important to the success of the project were employing competent, motivated staff, and providing resources, training and support for field workers.

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This study used an existing dynamic optimization model to compare costs of common treatment protocols and J5 vaccination for clinical mastitis in US dairy herds. Clinical mastitis is an infection of the mammary gland causing major economic losses in dairy herds due to reduced milk production, reduced conception, and increased risk of mortality and culling for infected cows. Treatment protocols were developed to reflect common practices in dairy herds. These included targeted therapy following pathogen identification, and therapy without pathogen identification using a broad-spectrum antimicrobial or treating with the cheapest treatment option. The cost-benefit of J5 vaccination was also estimated. Effects of treatment were accounted for as changes in treatment costs, milk loss due to mastitis, milk discarded due to treatment, and mortality. Following ineffective treatments, secondary decisions included extending the current treatment, alternative treatment, discontinuing treatment, and pathogen identification followed by recommended treatment. Average net returns for treatment protocols and vaccination were generated using an existing dynamic programming model. This model incorporates cow and pathogen characteristics to optimize management decisions to treat, inseminate, or cull cows. Of the treatment protocols where 100% of cows received recommended treatment, pathogen-specific identification followed by recommended therapy yielded the highest average net returns per cow per year. Out of all treatment scenarios, the highest net returns were achieved with selecting the cheapest treatment option and discontinuing treatment, or alternate treatment with a similar spectrum therapy; however, this may not account for the full consequences of giving nonrecommended therapies to cows with clinical mastitis. Vaccination increased average net returns in all scenarios.

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