Vaccination
and transmission -
Dr. Keith Sumption
Those
who say vaccination only prevents disease occurring and does not interfere
with transmission overlook some vital and fundamental points:
- 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.
- 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.
- 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.
- 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.
- 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
|
