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Vaccination and transmission

 

Those who say vaccination only prevents disease occurring and does not interfere with transmission overlook some vital and fundamental points:

 

  1. Disease is part of the transmission process; animals with lesions produce enormous quantities of virus which are easily transported off the contaminated site -for example cattle with clinical disease are expected to produce between 100,000 and perhaps 500,000 times more virus per day in saliva, mouth or feet lesions, than that produced by the aerosol route -a fact rather almost entirely overlooked. This is, of course, a reason why our control evolved to slaughter herds as quickly as possible after disease was recognised.

 

  1. Vaccination with killed antigens (the current vaccines) acts by production of serum antibodies; these prevent disease occurring (and hence cut the enormous liberation of virus) and are considered to prevent excretion of virus by milk (which can be at 40,000 times per day the amount shed by aerosols), urine and faeces. Hence a vaccinate exposed to an infected animal (a non-vaccinate) produces almost no virus -although some is produced as an aerosol from the head/throat. Experiments by Terpstra and colleagues in Holland (below) were conducted to determine whether a well vaccinated animal might spread infection to a NON-vaccinate stabled in the same shed -and drinking from the same bowl. They used doses of virus which are huge compared to an expected level that might occur by a vaccinated animal meeting infection "over the fence". The results show that transmission can occur, but at low rates and were only shown to occur with NON-vaccinates. In reality, if virus infection is a risk in the area, ALL animals on a farm would be advised to be vaccinated. Only ridiculous disease control strategists would advise vaccinating only a few animals on the farm (as occur in the experiments such as Terpstra's), or  mixing vaccinates and non-vaccinates when there is infection in the immediate area.

 

  1. Animals on UK farms are almost entirely kept in groups  (what we know as farms) with little or no animal movement between groups once movement controls are imposed; they are not mixing and milling about the countryside, in contrast to the usual situation with  people which epidemiologists are used to. Control has always  -in the last 100 years -been farm based. The basis of control is preventing virus spreading from one farm to another. Transmission of virus between animals on a farm is only, in principle, of any consequence if by this occurring it leads to spread to another farm. Significant spread within a vaccinated group is not expected; the chain of transmission might perhaps occur between a few animals, but then stop. In contrast in non-vaccinated farm the enormous virus output from diseased -or incubating animals -in forms that lead to contamination of people, fodder, vehicles, milk tankers, vets and other persons inspecting the animals - is extremely likely to lead to spread, with a risk of spread dependent on risk factors. In addition the aerosol production by non-vaccinates supports rapid intra-herd spread (and disease) , and potential over the fence spread. The latter is considered "uncontrollable spread" since virus shed by other routes in theory should stay "on the farm". In practice the enormous contamination produced by infected non-vaccinates can easily move off farm, inadvertently by people or before knowing it, by aerosols. 

 

 

  1. The British scientific response to FMD outbreaks has been characterised in the past (before 2001) by extreme interest in how virus moves off one farm and onto others. Past FMD inquiries dwelt at length on this aspect, and laboratory studies on virus production/susceptibility of animals, indicate to us how understanding the critical control points in virus escape from farms are vital in planning effective disease control measures. Into our understanding of how virus is likely to move off farms, we must add the findings that vaccinated animals produce little or any virus by routes that are expected to be involved in spread by people or objects. The above is consistent with vaccination being seen to be highly successful in emergency use in countries with poor levels of bio-security in relation to the UK.

 

  1. If a vaccine takes 4-5 days to lead to a strong level of immunity (i.e. at least  prevention of disease even if full effect on transmission has not yet been reached) then  vaccination can "get ahead" of the epidemic by ensuring that a sufficient number of farms are vaccinated 4-5 days ahead of anticipated first exposure to virus. Modelling can help in this by indicating where such farms are likely to be in relation to known infected premises, the known or anticipated rate of spread in the area in the coming days-weeks. Where uncertainty exists, larger ("blankets"- rather than "rings") may be required, the drawbacks being heavier use of vaccine, and more farms to survey after the last case has occurred before restrictions can be lifted. Of course farms closest to IP's will be at greatest risk and most concerned to protect themselves; since with precautions many of these will avoid infection for at least 4-5 days then vaccination close to known IP's gives a chance to gain protection before exposure occurs; albeit with less certainty, and with a risk that disease may occur within days of vaccination since some animals might be incubating infection at the time of vaccination. However these farms are the "front-line" in protection, and virus spread within such herds may be expected to occur only to limited extent where a significant number of animals are protected at the time when a herd-mate becomes exposed.

 

Additional information on vaccination and transmission

Impact on within farm transmission -experiments in cattle (see Terpstra et al, 1990)

n     Field vaccinated cattle 1,2 &3 years post-vaccination challenged with huge dose (80 times natural pig challenge over 24hrs)

n     tethered with NON-vaccinate - drink at same bowl

n     Only 1 of 30 vaccinates transmitted (<25 mo Post-vaccination)

n     5 of 30 vaccinated 32-38 mo previously

n     8 of 20 (40%) transmitted after heterologous strain challenge, 9-10 mo post-vaccination

 

Lessons from Terpstra

n      Transmission by vaccinates is low level and low frequency (and of course, short-lived- days)

n      No clinical disease in vaccinates when vaccine matched to challenge, and rare in -contact susceptibles - vaccinates emit a low dose that rarely infects in-contacts

n      Non-vaccinated controls developed severe FMD

n      3/10 vaccinated animals developed FMD where index of antigenic similarity (R value) of vaccine differed (0.25) from virus challenge -since vesicles (disease) will result in high virus shedding, preventing disease is important

 

Supporting work with high payload emergency vaccines:

n     Salt et al, 1998 - pigs (no transmission >7 days post-immunisation)

n     Sheep -Cox et al, 1999

n    4 hr severe airborne challenge -Asia 1 or C, short intervals (3-10 d) vaccination to challenge

n    Asia 1; transmission to 3/8 sheep in contact with vaccinates (100% in control group)

n    Type C; transmission to 0 of 8 (2/2 in controls)

n    in 3 expts  0 of 48 vaccinates had viraemia or lesions (8/10 controls had viraemia)

 

Practical lessons from transmission experiments with vaccinated animals

n      Don't mix vaccinates and non-vaccinates  when risk of acute virus infections (cases) in the neighbourhood!

n      Vaccinate all animals on a farm  - the experiments used non-vaccinates as "indicators"  - in reality all susceptible animals on a farm would/should be vaccinated in an emergency campaign

n      People who argue that vaccination does not prevent transmission are not considering the farm based nature of European control

 

 

Transmission of virus within a vaccinated group

n      No published experiments to support or refute this; never been studied since those involved with FMD vaccine trials have simply not thought it a question that needs to be asked

n      logical to expect that if a vaccinate were to receive virus from an infected vaccinate (e.g. the latter being an animal which was infected by a non-vaccinated, infected animal "over the fence" from a contiguous IP) then the worst that can be expected is some virus multiplication in the throat but not excretion of virus by other routes. Such an animal would itself be extremely unlikely to infect another animal, and so the chain dies out within that farm. Spread to another farm would be exceptionally unlikely as heavy virus contamination would not occur since the vaccinates produce little, if any, virus in excretions/milk.

n      Evidence of this comes from field studies following emergency vaccination -there is no evidence of spread under vaccination after cases cease - survey following emergency vaccination usage in Albania, 1996