Rabies

Rabies
Rabies - History
• Rabies has been known since around 2000 B.C.
• Rabies appears to have originated in the Old World, the
first epizootic in the New World occurring in Boston in 1768.It spread
from there, over the next few years, to various other states, as well as
to the French West Indies, eventually becoming common all across
North America.
• More than 99% of rabies cases in countries where dogs commonly
have the disease are caused by dog bites
• Rabies caused about 17,400 deaths worldwide in 2015. More than
95% of human deaths caused by rabies occur in Africa and Asia.
Rabies – Treatment and pervention
• Treatment after exposure can prevent the disease if administered
promptly, generally within 10 days of infection.
• Animal control and vaccination programs have decreased the risk of
rabies from dogs in a number of regions of the world.
• So that’s why it is most wanted to know how the epidemic is spread
so It will be more efficient to vaccinate against it.
• And fot this we will use math
Simple Model for the Spatial Spread of an
Epidemic
• We assume the population consists of only two populations,
infectives I(x,t) and susceptibles S(x,t) which interact.
• Now, I and S are functions of the space variable x as well as time.
• We model the spatial dispersal of I and S by simple diffusion with
coefficient D.
• As before we consider the transition from susceptible to infectives to
be proportional to rSI.
• And the infectives has mortality rate aI, 1/a is the life expectancy of
an infective.
Epidemic
• With all this assumptions we get the following:
𝑑𝑆
• = −𝑟𝐼𝑆 + 𝐷∇2 𝑆
𝑑𝑡
𝑑𝐼
• = 𝑟𝐼𝑆 − 𝑎𝐼 + 𝐷∇2 𝐼
𝑑𝑡
• a ,r, D are positive constants.
• Here we consider only the one-dimensional problem.
• Let us denote by S0 the initial homogeneous susceptibe density
• We nondimensionalize ths system by writing:
𝐼 𝑆 𝑟𝑆0 1/2 𝑎
• 𝐼∗ = , 𝑆∗ = , 𝑥∗ = ( ) 𝑥, 𝑡 ∗ = 𝑟𝑆0 𝑡, 𝜆 =
𝑆0 𝑆0 𝐷 𝑟𝑆0
Epidemic
• After droppint the * we get:
𝑑𝑆 𝑑2 𝑆
• = −𝐼𝑆 + 2
𝑑𝑡 𝑑𝑥
𝑑𝐼 𝑑2 𝐼
• = 𝐼𝑆 − 𝜆𝐼 + 2
𝑑𝑡 𝑑𝑥
• 1/𝜆 is the basic reproduction rate of the infection.
• The specific problem we investigate here is the spatial spread of an
epidemic wave of infectiousness into a uniform population of
susceptibles.
Epidemic
• We want to determine the conditions for the existence of such a traveling
wave and what his speed will be?
• So we will look for wave solutions we will use z=x-ct
• 𝐼 𝑥, 𝑡 = 𝐼 𝑧 , 𝑆 𝑥, 𝑡 = 𝑆 𝑧
• Where c is the wave speed. Substituting this we will get:
• 𝐼 ′′ + 𝑐𝐼 ′ + 𝐼 𝑆 − 𝜆 = 0, 𝑆 ′′ + 𝑐𝑆 ′ − 𝜆𝐼𝑆 = 0
• When we differentiate with respect to z.
• So we have eigenvalue problem so we can find the range of values of
lambda such that a solution exists with positive wave speed and
nonnegative I and S such that:
• 𝐼 −∞ = 𝐼 ∞ = 0,0 ≤ 𝑆 −∞ < 𝑆 ∞ = 1
Epidemic
Here is an example of Epidemic wave:
Epidemic
• Let us solve this equation
• 𝐼′′ + 𝑐𝐼′ + 𝐼 𝑆 − 𝜆 = 0, 𝑆 ′′ + 𝑐𝑆 ′ − 𝜆𝐼𝑆 = 0
• We will linearise where S->I , I->0 to get:
• 𝐼′′ + 𝑐𝐼′ + 1 − 𝜆 𝐼 ≈ 0
• Which solutions are:
• 𝐼 𝑧 ∝ exp[−𝑐 ± {𝑐 2 − 4 + 4𝜆}1/2 ]
• Since we want I to be nonnegative, the wave cannot oscillate about
I=0. so there must hold:
• 𝑐 ≥ 2(1 − 𝜆)1/2 , 𝜆 < 1
Epidemic
• so if 𝜆 > 1 then there is no wave solution exists so this is the necessary
threshold condition for the propagation of an epidemic wave. Thus:
𝑎
•𝜆= >1
𝑟𝑆0
𝑎
• So we see that there is a minimum critical population density 𝑆𝑐 = for an
𝑟
epidemic wave to occur.
• On the other hand with a given transmission we get a threshold mortality
rate 𝑎𝑐 = 𝑟𝑆0 which if exceeded prevents an epidemic.
• So if we can by isolation, medical intervention and so on reduce the the
transmission factor r of the disease it may be possible to violate the
condition and hence prevent ths spread of the epidemic.
The Spatial Spread of Rabies I
• During the past few hundred years, Europe has been repeatedly
subjected to rabies epidemics. It is not known why rabies died out 50
or so years before the current epidemic started. We will try to give a
possible scenario for this.
• The present epizootic seems to have started about 1939 in Poland
and it has moved steadily westward at a rate of 30-60 km per year. It
has been slowen down by barriers such as rivers, mountains and
autobahns.
• It is important to understand how the rabies epizootic wave front
progresses into uninfected regions, what control methods might halt
it and how the various parameters affect them.
• Again we have 2 populations S and I which interact with each other
and depends on the space variable x and on time t.
• We will make now the assumption that the virus cause behavioral
changes in the fox and make him lose its sense of territory and the fox
wanders randomly.
• So we will assume that only the infectives are dispersing with
diffusion constant D. We get:
𝑑𝑆
• = −𝑟𝐼𝑆
𝑑𝑡
𝑑𝐼
• = 𝑟𝐼𝑆 − 𝑎𝐼 + 𝐷∇2 𝐼
𝑑𝑡
• After nondimensionalization the system becomes:
𝑑𝑆
• = −𝐼𝑆
𝑑𝑡
𝑑𝐼 𝑑2 𝐼
• = 𝐼𝑆 − 𝜆𝐼 +
𝑑𝑡 𝑑𝑥 2
𝑎
• 𝑤ℎ𝑒𝑟𝑒 𝜆 = is a measure of the mortality rate as compared with
𝑟𝑆0
the contact rate.
• Travelling wave fronts solutions are of the form:
• 𝐼 𝑥, 𝑡 = 𝐼 𝑧 , 𝑆 𝑥, 𝑡 = 𝑆 𝑧
• And we get:
• 𝐼′′ + 𝑐𝐼′ + 𝐼 𝑆 − 𝜆 = 0, 𝑐𝑆 ′ = 𝐼𝑆
• 𝐼 −∞ = 𝐼 ∞ = 0, 𝑆′(−∞) = 0, 𝑆 ∞ = 1
• Note that it is the derivative of S which tends to 0 as z goes to minus
infinity, since we anticipated a residual number of susceptibles foxes
to survive the epidemic.
• Again after linearization around I=0 and S=1 we find the same
requirement for the wave speed:
• 𝑐 ≥ 2(1 − 𝜆)1/2 , 𝜆 < 1
• Now we take the analysis further, we extract
𝑐𝑆′
•𝐼= and substitute this we get:
𝑆
𝑐𝑆′
• 𝐼 ′′ + 𝑐𝐼 ′
+ 𝑆−𝜆 =0
𝑆
• We integrate and get:
• 𝐼 ′ + 𝑐𝐼 + 𝑐𝑆 − 𝑐𝜆𝑙𝑛𝑆 = 𝑐𝑜𝑛𝑠𝑡𝑎𝑛𝑡
• Using the boundary condition as z->infinity we get S=1,I=0,I’=0 we get the
constant is c
• 𝐼′ + 𝑐𝐼 + 𝑐𝑆 − 𝑐𝜆𝑙𝑛𝑆 = 𝑐
• Now using the boundary condition as z->-infinity we get ,I=0,I’=0 thus
we get transcendental equation for the surviving susceptibles
population 𝜎
• 𝜎 − 𝜆𝑙𝑛𝜎 = 1
𝜎−1
•𝜆= <1
𝑙𝑛𝜎
• Thus 0 < 𝜎 < 𝜆 < 1
• The smaller lambda the fewer susceptible survive, in other words the
worse the epidemic:
• When rabies does persist, that is lambda<1 the computed speed of
the propagation of the epidemic wave is the minimum of the
allowable speeds, 𝑐 = 2(1 − 𝜆)1/2 = 2[𝐷(𝑟𝑆0 − 𝑎)]1/2
• For example for 𝜆 = 0.5
• The wave speed is 𝑐 = 2
• Let us compare the qualitative form of the susceptible fox population
with that obtained data from continental Europe.
• There are big differences between the two waves.
• Because our model is only covers the passage of an epidemic front,
clearly after the passage of the wavefront the susceptible population
will start to increase again since the foxes find themselves in an
environment which admits a larger carrying capacity.
• In other words our model has a short time scale, so we want to
improve him so we add a term for the fox reproduction.
• We model this by a simply logistic growth and the equation becomes:
𝑑𝑆 𝑆
• = −𝑟𝐼𝑆 + 𝐵𝑆(1 − ) where B is the linear growth rate
𝑑𝑡 𝑆0
• Again with nondimensionalization we get:
𝑑𝑆
• = −𝐼𝑆 + 𝑏𝑆(1 − 𝑆)
𝑑𝑡
𝑑𝐼 𝑑2 𝐼
• = 𝐼𝑆 − 𝜆𝐼 + 2
𝑑𝑡 𝑑𝑥
• And now we get the following epidemic wave:
• Now there is a good qualitative comparison between the results from
this model and the data recored in Europe.
• The oscillations are decaying and eventually S → 𝜆 and 𝐼 → 𝑏(1 − 𝜆)
The Spatial Spread of Rabies II
• Now we consider a 3-species model that purposed by Murray and
Anderson
• SIR model in which we divide the fox population into susceptible
foxes S, infected but not infectious I, and infectious R
• The need for 3 species is based on the long incubation period of 12 to
150 days that the rabies virus undergoes in the infected animal.
• The dynamics of the fox population in the absence of rabies can be
approximated by:
𝑑𝑆 𝑆
• = 𝑎 − 𝑏 𝑆(1 − )
𝑑𝑡 𝐾
• a – linear birth rate, b- intrinsic death rate, K- environmental carrying
capacity, we take them to be constant altought they may difer by the
habitat.
• Under out assumptions we get that the population with rabies is:
𝑑𝑆 𝑆
• = 𝑎−𝑏 𝑆 1− − 𝛽𝑅𝑆
𝑑𝑡 𝐾
• Now we assume that Infected foxes become infectious at an average
1
per capita rate 𝜎 where is the average incubation time. Rabies is
𝜎
invariably fatal, with rabid foxes dying at an average per capita rate 𝛼,
1
where is the average duration of clinical disease.
𝛼
• Again we assume that rabid foxes are confused and lose their sense of
direction and territorial behavior and wandering randomly, this is the
main cause of the spatial spread of the disease.
• Under all this assumptions we get the following system:
𝑑𝑆 𝑎−𝑏 𝑁𝑆
• = 𝑎−𝑏 𝑆− − 𝛽𝑅𝑆
𝑑𝑡 𝐾
𝑑𝐼 𝑎−𝑏 𝑁𝐼
• = −𝑏𝐼 − + 𝛽𝑅𝑆 − 𝜎𝐼
𝑑𝑡 𝐾
𝑑𝑅 𝑎−𝑏 𝑁𝑅 𝑑2 𝑅
• = −𝑏𝑅 − + 𝜎𝐼 − 𝛼𝑅 + 𝐷 2
𝑑𝑡 𝐾 𝑑𝑥
• Where the total population N=S+I+R
• We may notice that in the absence of spatial spread we would get:
𝑑𝑁 𝑎−𝑏 𝑁2
• = 𝑎−𝑏 𝑁−
𝑑𝑡 𝐾
• Which is the equivalent logistic form for the total population
• We have written the equations in one-dimensional form but we shall
use the full 2-dimensional form when we apply the model to the
spread of the disease on England.
• Anderson calculate the parameters for rabies among foxes and got:
• The spatialy homogeneous steady state solutions other than the sero steady state
is given by:
𝑎+𝑏 𝛽𝐾+ 𝑎−𝑏 𝛼+𝑎 [𝜎𝛽𝐾 𝜎+𝑏 +𝛼(𝑎−𝑏)(𝜎+𝑎)]
• 𝑆0 =
𝛽[𝜎𝐵𝐾−𝑎(𝑎−𝑏)]2
[𝛽𝐾 𝑎+𝑏 +(𝑎−𝑏)(𝜎+𝑎)]𝑅0

• 𝐼0 =
[𝜎𝐵𝐾−𝑎 𝑎−𝑏 ]
(𝑎−𝑏)[𝜎𝛽𝐾−(𝛼+𝑎)(𝜎+𝑎)]𝑅0
• 𝑅0 =
𝛽[𝜎𝐵𝐾−𝑎 𝑎−𝑏 ]
• We get a critical carrying capacity 𝐾𝑇 which is given by the condition for a
nonzero value for the steady state R0
(𝜎+𝑎)(𝛼+𝑎)
• 𝐾𝑇 =
𝛽𝜎
• In the spatially uniform situation(D=0) when rabies is introduced into a
stable population of halthy foxes two possible behaviours are possible:
• 1. 𝐾 < 𝐾𝑇 and then the epidemic threshold value of the carrying capacity,
rabies eventually disappears (R->0,I->0)
• From epidemiological evidence, rabies seems to die out if the carrying
capacity is somewhere between 0.2 and 1.0
• 2. 𝐾 > 𝐾𝑇 and then we get an equilibrium persistence,p , of rabies, where
𝑅0 +𝐼0
𝑝=
𝑆0 +𝐼0 +𝑅0
• From the date from the table we get p=0-4% and this agrees with
epidemiological evidence
• In the spatially uniform situation(D=0) when rabies is introduced into a
stable population of halthy foxes two possible behaviours are possible:
• 1. 𝐾 < 𝐾𝑇 and then the epidemic threshold value of the carrying capacity,
rabies eventually disappears (R->0,I->0)
• From epidemiological evidence, rabies seems to die out if the carrying
capacity is somewhere between 0.2 and 1.0
• 2. 𝐾 > 𝐾𝑇 and then we get an equilibrium persistence P , of rabies, where
𝑅0 +𝐼0
𝑝=
𝑆0 +𝐼0 +𝑅0
• From the date from the table we get p=0-4% and this agrees with
epidemiological evidence
• We also want to analyse the wavefront of the system and find their speed
of propagation in order to understand how fast the rabies spread.
• Again we will use nondimensionalization and we get the following system:
𝑑𝑠
• = 𝜀 1 − 𝑛 𝑠 − 𝑟𝑠
𝑑𝑡
𝑑𝑞
• = 𝑟𝑠 − 𝜇 + 𝛿 + 𝜀𝑛 𝑞
𝑑𝑡
𝑑𝑟 𝑑2 𝑟
• = 𝜇𝑞 − 𝑑 + 𝜀𝑛 𝑟 + 2
𝑑𝑡 𝑑𝑥
• 𝑛 =𝑠+𝑞+𝑟
• We are searching for wave solution to the system which travel at a
constant velocity v into an undisturbed, rabies-free region. We will
look at the variable 𝜉 = 𝑥 + 𝑣𝑡 , v is the speed of the wave.
• After some algebra it transform into eigenvalue problem which has 4
eigenvalues 𝜆1 , 𝜆2 , 𝜆3 , 𝜆4 and each wave is of the form:
𝑤𝜉 𝑤𝜉
• 𝑠 − 𝑠0 ~ 𝐴𝑐𝑜𝑠 + 𝐵𝑠𝑖𝑛 exp(−𝜆𝜉/𝑣)
𝑣 𝑣
𝑤𝜉 𝑤𝜉
• q−𝑞0 ~𝑤/𝜇 𝐴𝑠𝑖𝑛 − 𝐵𝑐𝑜𝑠 exp(−𝜆𝜉/𝑣)
𝑣 𝑣
𝑤𝜉 𝑤𝜉
• r−𝑟0 ~𝑤/𝑑 𝐴𝑠𝑖𝑛 − 𝐵𝑐𝑜𝑠 exp(−𝜆𝜉/𝑣)
𝑣 𝑣
• Now for the numerical simulation of the model mechanism:
Control strategy
• We discuss here one possible control strategy as developed by
Murray. Of possible protective barrier against the rabies epizootic.
Which can be achieved by reducing the susceptible fox population
below the critical density 𝐾𝑇 in areas ahead of the advancing wave.
• Such a barrier can be created by killing or vaccination. Since killing
releases territories, there could be a more rapid colonization by
young foxes which could in fact enhance the spread of the disease.
Vaccination cause less disruption in the ecology and is probably even
more economic.
Control strategy
• So we want to put a break so he could stop the outbreaks. We notice that
each outbreak of the disease is followed by a long quiescent period during
which very few cases of rabies occur. The spatial and temporal dimensions
are such that the secondary epidemic wave is sufficiently far behind so that
the first wave will either have moved past the break or have effectively
died out by the time the second one arrives. So it seems reasonable to
assume that all the same population reduction schemes which eradicate
the first outbreaks will also be effective in stopping all subsequent
outbreaks from passing through. Thus we try to wide the break in order to
stop the first outbreak.
• Since the aim of any control scheme is to keep the density of foxes small,
we treat the break region as one with a carrying capacity below 𝐾𝑇
Control strategy
Control strategy
• This shows what happens when the epizootic wave coming in from the left,
impinges on the break region. As the infection wave moves into the region
x>0 it spreads out, decays in amplitude and the total number of infected
foxes decreases.
• Eventually there will be less than p infected foxes/km^2 remaining. Let
𝑡𝑐 (𝑝) be the time at which this occurs. We now choose p sufficiently small
that the probability of a rabid fox encountering susceptible one after this
critical time is neglible.
• Now since the wave cant propagate in the break region it simply decays. So
we choose the width of the break to be the point 𝑥𝑐 where the infected fox
density is a given small fraction m of the value at the origin, it means:
• 𝐼 + 𝑅 𝑥𝑐 , 𝑡𝑐 = 𝑚[(𝐼 + 𝑅)(0, 𝑡𝑐 )]
Control strategy
• And the dependence of the break width in terms of the percentage
population reduction in the break:
Two dimensional epizootic
• In general fox population are not uniform, but instead vary according
to the hospatlity and carrying capacity of the local environment.
• We first present the results of what happens when the epizootic wave
encounters a localized region of different carrying capacity from the
surrounding environment. The model is the same as before only now
the diffusion term is replaced by 𝐷∇2 𝑅 , and we assume that the
carrying capacity K and the initial susceptible fox density are equal to
uniform value everywhere on a square region, except for a small path
in the center, where they have different values. We now introduce a
uniform distribution of rabid foxes along one edge of the square. The
solution numerically is:
Suceptible
Rabid
• We see that the front moves faster through the region of higher
carrying capacity as we would expect.
• The residual fox population, once the first outbreak has moved past,
is slightly lower in the pocket of higher K than in the surrounding
region.
• We also see that the pocket of lower susceptible fox density provides
a sort of protection to the region just adjoining it.
• England has remained rabies free due mainly to the strict quarantine laws
and high public awareness of the potential dangers. But the proximity to
north France and the increased private boat traffic between continental
Europe and Britain it seems inevitable that the disease will be brought into
Britain in the near future,and it will be serious because there is a high
density of foxes, both urban and rural in England. So appearance of rabies
there is very risky. If no control measures are applied the epidemic would
move quickly through England.
• We can use the model here to obtain a rough estimate for the position of
the epidemic front after rabies is introduced to the fox population.
• Macdonald gives a map of estimated fox densities in England.
• Now we may apply our model of introducing the rabies into England
and we will get the following
• Just as in the uniform density case, most of the case of rabies are
concentrated in a narrow band at the front.
• The susceptible population is effectively decimated by the epidemic
and partially regenerates before another wave starts again.
• We see that the second outbreak starting off from Southhampton
about 7 years after the first one.
• These quantitive predictions are only rough estmates, and Macdonald
emphasizes that the fox densities in his map are only educated
guesses. And not enough is known about the behavior of rabid foxes
to obtain a sharp estimate for the diffusion constant.
• We have also neglected such geographical factors as rivers, which
tend to provide a channel for the epidemic, speeding its movement.
• However this model provides a plausible quantitive first estimate for
the progression of rabies in England if the epidemic was allowed to
move unchecked. The model also provides a means of estimating
realistic breaks widths which would seriously impede the spread of
the disease.
Summary
• The question of what method should be used to contain an outbreak is
interesting. The model suggests that vaccination would be more effective than
gassing or poisoning since the farmer would help to restrict the spread of
infective foxes whereas the latter would enhance the spread.
• The probability that rabies will eventually reach England is high, so it is very
important to understand as much as possible about the disease, its transmission
and how it spreads well before it arrives.
• Perhaps the most disturbing aspect of these results is the rapidity with which the
epidemic would move through the central region, at speeds of around 100
km/year.
• No less disturbing is the reappearance of the disease several years after the
passage of the epidemic front.
• We have been primarily concerned here with the spatial propagation of an
epidemic.

Rabies

Hochgeladen von

Dokumentinformationen

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Rabies

Hochgeladen von

Copyright:

Verfügbare Formate

Rabies

[𝛽𝐾 𝑎+𝑏 +(𝑎−𝑏)(𝜎+𝑎)]𝑅0

Das könnte Ihnen auch gefallen