Discussion on a selection of key scientific articles

 

Three interesting articles have been selected for discussion. Regulatory changes in Japan help speed the response to antigenic drift in influenza viruses, with MAFF and vaccine manufacturers working together to bring new vaccine strains to the market quicker. A field trial in Turkey evaluates responses to FMD vaccines, showing that the correct implementation of vaccination has a big impact on immunity. A review of papers on rabies vaccination in Africa demonstrates that it is possible to access a large proportion of dogs and have a real impact on this disease for both animals and humans.

Introduction of an update system for vaccine strains of veterinary influenza vaccines in Japan, Biologicals, 43 pp. 150-152, Gamoh, K., Nakamura, S., 2015.

A constant difficulty in the use of vaccines against avian and equine influenza is the antigenic drift of the virus. In order to keep pace with changes in field virus, vaccine strains should be updated regularly, but veterinary regulation and registration often mean that it can take several years for a new vaccine strain to be introduced. In Japan, the Ministry of Agriculture, Forestry and Fisheries (MAFF) has addressed this by establishing a vaccine strains selection committee that assesses currently available strains and advises on the most appropriate strains to use.

Approaches to avian and equine influenza have to differ, owing to contrasting needs when considering disease control. For avian influenza, the main countermeasures rely on early detection and culling, with vaccination potentially interfering with surveillance, so that vaccination is only an option if the disease gets out of hand. However, for equine influenza, vaccination has been demonstrated to be an effective tool in the control of the disease. Despite these differences, all influenza vaccines must be up to date and include relevant strains so that they do provide protection if required.

In a novel approach to the difficulties arising from the Pharmaceutical Affairs Law in Japan, which normally result in the development-to-market phase of new vaccine strains taking several years, the MAFF have changed regulations so that influenza viruses are treated in a unique manner. In this case, MAFF establishes the strains and distributes them to the market authorization holder, and there is no requirement to register newly updated vaccines. This reduces development-to-market to approximately 1 year.

This update system shows good cooperation between pharmaceutical companies and the Japanese government. It allows a more rapid response to the changing needs of influenza control while not placing excessive burden on the market authorization holders.

Key thoughts: Transboundary and emerging diseases are often “niche” areas for pharmaceutical companies and do not command the same levels of investment as more commercially driven diseases. In addition, a quick response is often required in order to react to changing field situations. However, by working together, governments and manufacturers can find novel approaches that continue to maintain safety while allowing the development of products that can improve health.

Randomised field trial to evaluate serological response after foot-and-mouth disease vaccination in Turkey, Vaccine, 33 ( 6 ) pp. 805 – 811, Knight-Jones, T.J.D., Bulut, A.N., Gubbins, S., Stärk, K.D.C., Pfeiffer, D.U., Sumption, K.J., Paton, D.J., 2015.

 Vaccination programmes do not always achieve the expected, and hoped-for, results. Although the blame is often placed on the vaccine, in fact there are a large number of reasons why programmes may appear not to work. In Anatolian Turkey FMD has remained uncontrolled despite years of mass vaccination. There are a number of possible reasons behind this, and the evaluation of serological responses can aid our understanding of these further.

A complication with FMD vaccination and control programmes has always been the relatively short-lived immunity. While vaccines have improved, it is still necessary to vaccinate twice a year. In addition, for this to be effective, an initial course of two vaccinations a month apart is required. Unfortunately, vaccination programmes often miss out on this initial priming course. The use of FMD vaccine is further blurred by the different requirements of outbreak control vs endemic settings and the use of low- vs high-potency vaccines, with low-potency vaccines providing limited protection.

The randomized field trial in this study looked at 98 households in 23 villages from eight provinces. The households were visited twice, approximately three months apart, and blood samples taken from the cattle. All bar one of the farms were traditional small-holdings, with the remaining unit being a commercial dairy farm. Those animals that were positive for nonstructural protein were discarded from the study.

A major finding was the significant and sizable impact of having a two-dose primary course. With the animals sampled, it appeared that they did not mount a strong and longer-lasting immune response before they had received three vaccinations. This suggests that without the initial vaccinations approximately a month apart, it appears that young animals will remain unprotected for a large proportion of the year. A properly completed primary course may incur additional costs, but the protection in animals under 20 months old is greatly improved.

This study was looking at the impact of a low-potency vaccine. While high-potency vaccines will perform better, producing broader and longer-lasting protection, the basic concept remains the same, ie, if vaccines are not used properly and according to the manufacturer's guidelines, then the results achieved will not be as good as hoped for. Inappropriately used vaccines present a real danger because vets and farmers can end up relying on the fact the animal is vaccinated and not undertake proper controls.

Key thoughts: Short-term savings in vaccination programmes may have long-lasting, detrimental effects that are unseen at the time. Immune responses are complex and need to be properly primed in order to achieve the desired levels of protection. When outbreaks continue despite vaccination, then the farmer can lose confidence in the process, and this can have a negative impact on future compliance to schemes. High-potency vaccines, used at appropriate intervals, will provide the best protection possible and have an improved impact on FMD disease control.

Review on dog rabies vaccination coverage in Africa: A question of dog accessibility or cost recovery?, PLoS Neglected Tropical Diseases, 9 ( 2 ) art. no. e000344713, Jibat, T., Hogeveen, H., Mourits, M.C.M., 2015.

Rabies continues to be a significant human health problem, and in Africa the majority of human cases result from dog bites. For this reason the vaccination of dogs is proposed as the most effective method to control the disease in humans. This article undertook a review of research articles in order to assess the impact and the cost benefits. Two key findings have a significant impact on the future approach to rabies control. The first is that the majority of dogs in Africa are owned. The second is that a “free of charge” vaccination scheme can achieve vaccination rates of around 68%, which is close to the WHO-recommended coverage.

Rabies has a high fatality rate in humans—almost 100% once signs are observed. Rabies has been cited as causing over 60,000 human deaths each year, with more than 95% of these deaths occurring in Africa and Asia. Approximately 15 million people receive post-exposure prophylaxis (PEP) annually, representing a considerable human health cost. Owing to both cost and geographical location, PEP is often not even accessible to many in Africa.

While vaccination of dogs has been put forward as an ideal route to control the disease and prevent rabies in humans, there has been an assumption that catching and restraining dogs is an insurmountable hurdle. However, as attitudes have changed and dogs are often referred to as “free roaming” as opposed to "stray," it has become necessary to revisit these views. Dog ownership is an essential part of the success of any campaign.

To gain further insights for this paper, a systematic search was made in journal databases for a number of related themes, resulting in 1239 articles. Once duplicates were removed and publications not fulfilling the selection criteria were excluded, then 16 articles published between 1990 and January 2014 were collated and data gathered in Microsoft Excel for analysis. This data was used to gain a better understanding of dog demography, and meta-analysis allowed evaluation of the impact of financial arrangements on the success of vaccination campaigns.

The demography results challenge popular perceptions regarding dogs in Africa. Up to 98% of dogs are owned. While these dogs may be kept for socio-economic reasons, including guarding and hunting, they are also kept as pets. Eleven  countries were represented in the review, and all except Tanzania reported that over two thirds of the dogs had owners. Puppies under 3 months of age constituted up to 30% of the dog population, with the mean age of dogs varying between 1.8 and 3.4 years.

For the success of vaccination campaigns, there was a significant difference between free and owner-charged groups. Although the coverage in the charged groups was less than 50%, in the free campaigns then coverage was around 68%.

Studies indicate that only a small proportion of bites come from dogs that are considered ownerless. Therefore, overall, the indication is that vaccination campaigns in Africa can reach enough animals to have an impact on the circulation of rabies and the risk to humans.

Key thoughts: Previous assumptions about dog populations and accessibility need to be reassessed to ensure that we properly understand dog dynamics. More dogs have owners than previously thought, and this has led to a change in terminology, referring to “free roaming” dogs rather than “strays”. This better reflects the situation in many countries. Of concern is that where the owners have to pay towards vaccination, even with partial payments, then there is a significant reduction in uptake. This suggests that more focus needs to be placed on education so that the owners understand the needs and the benefits of vaccination.

 

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