A Discrete-Time Model with Vaccination for a Measles Epidemic

L. J. S. ALLEN, M. A. JONES, AND C. F. MARTIN Department of Mathematics, Texas Tech University, Lubbock, Received 30 May 1990; revised 26 November 1990

Texas 79409

ABSTRACT A discrete-time, age-independent SIR-type epidemic model is formulated and ana-

lyzed. The effects of vaccination are also included in the model. Three mathematically important properties are verified for the model: solutions are nonnegative, the population size is time-invariant, and the epidemic concludes with all individuals either remaining susceptible or becoming immune (a property typical of SIR models). The model is applied to a measles epidemic on a university campus. The simulated results are in good agreement with the actual data if it is assumed that the population mixes nonhomogeneously. The results of the simulations indicate that a rate of immunity greater than 98% may be required to prevent an epidemic in a university population. The model has applications to other contagious diseases of SIR type. Furthermore, the simulated results of the model can easily be compared to data, and the effects of a vaccination program can be examined.

1.

INTRODUCTION

A discrete-time, age-independent epidemic model with n subgroups is formulated and analyzed, then applied to a measles epidemic on a university campus. The model is of SIR type and generalizes a model formulated by Rvachev and Longini [24] for the global spread of influenza. The effects of vaccination are included in the model, and the model is developed for a localized epidemic (applicable to a university setting). Therefore, the original model of Rvachev and Longini [24] was modified accordingly. The effects of age are generally considered in measles models (e.g., [3, 6, 14, 15, 22, 23, 251. However, the age distribution of our population (university students) is limited primarily to 17-24-year-olds [2], and therefore age is not very significant. The effects of vaccination have been considered in measles models, but generally for continuous-time models (e.g., [3-6, 11, 15-17, 231. One advantage of a discrete-time model over a continuous-time model is the ease with which data can be compared to the simulated
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L. J. S. ALLEN,

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results. Since our goal is to compare the simulated results of the model to data from a measles epidemic, the probability that an individual is vaccinated is calculated using data for the number of individuals vaccinated. The general model will be formulated and discussed in Section 2. In Section 3 it will be shown that the model satisfies mathematical properties typical of SIR epidemic models; that is, solutions are nonnegative, the population size remains constant over time, and the epidemic concludes with all individuals either remaining susceptible or being removed from the infection process by acquiring immunity (through vaccination or natural immunity by having had the disease). In Section 4 data for a measles epidemic on a university campus will be compared to simulated results of the model. The model is used to estimate (for our population) the rate of immunity necessary to prevent an epidemic.
2. MODEL

The model is divided into five disjoint disease states for each of the n subgroups. The states are defined as follows:

Si(t)
Ei(7, t)

= number
= number

of susceptible of individuals

individuals on day t on day t who were exposed on

Ai(7, t> Ii(7, t) Ri(t)

day t--7 = number of asymptomatic but infectious individuals on day t who were exposed on day t - r = number of symptomatic and infectious individuals on day t who were exposed on day t - T = number of individuals who are removed from the infection process by immunity or isolation on day t,

where i=l,2,... , n and it is the number of subgroups. The model is similar to the one developed by Rvachev and Iongini [24] but includes an additional state, Ai, the number of individuals who are infectious but not yet showing any symptoms. Measles is contagious l-2 days before the onset of symptoms (e.g., fever) and 3-5 days before the appearance of a rash [lo]. A case of measles is reported only after the appearance of fever or rash. The number of individuals who transfer from state Ai to state Zi on day t represents the number of measles cases that are reported on day t. This provides a comparison between simulated results and data on the number of reported cases. In a manner similar to the derivation given in [24], four discrete probability distributions are defined for the probability that an individual is in one of the four disease states Ei, Ai, Zi, and Ri. From these probability

DISCRETE-TIME MODEL

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distributions three transition probabilities are defined that represent the transition probabilities between these four states. Let 1r,J2, -8s be random variables that represent the length of an individuals latent period, the length of an individuals latent plus asymptomatic period, and the length of an individuals latent plus infectious period, respectively. Let ~2 represent a set of individuals who were initially infected at the same time. The disease states of individuals in set & form a partition with discrete probability distributions defined as fG= ~(-8~ > 4, g(7) = P<-q =G 7 < Jz), h(T) = P<=z?z < 7 < -f3),
k(T) = PC-83 < T),

7=&l 7=0,1
7=&l 7=&l

,...) T,, ,...,72,

, . . . ,739 , . . . ,T3 + 1,

where f,g,h, and k represent the fractions of total individuals who are in the latent, infectious and asymptomatic, infectious and symptomatic, and removed states, respectively, and S(T)+ g(T)+ h(T)+ k(T) = 1. The values of 71, 72, and 73 are the maximum lengths of the latent period, latent plus asymptomatic period, and latent plus infectious period, respectively. It is assumed that f(O) = 1, since the latent period lasts at least 1 day; therefore, g(0) = h(O) = k(O) = 0. Using the above probabilities, the following three transition probabilities can be derived:

=f(T)-ff(T+l)

f(T)
=

f(T) > 0,

T=o,l

,...,Tl

g(T)--(T+l)+f(T)-fS(T+l) g(T)
<
7 + 11-52 4 T < -f3)

g(T)>&

7=&l

,...,72

y(T) = P( /3 =

kc + 1)- k(T) h(T)

h( 7) > 0,

7=&l

,...,Tj.

Thus p(T) is the probability that a latent individual becomes infectious on day 7 + 1, given that the individual was still latent on day T. The function 8(T) is the probability that an infectious individual becomes symptomatic on day 7 + 1, given that the individual was infectious but asymptomatic on day T. The function Y(T) is the probability that an infectious individual is removed from the population on day T + 1, given that the individual was symptomatic on day T.

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Now we will calculate the probability that a susceptible individual Sj becomes infectious at time t. This calculation represents an important difference between our model and the model formulated by Rvachev and Longini [24]. The difference is due to the fact that our model represents a localized epidemic; the infection is generally initiated by contact with individuals outside of the population being modeled. The probability that a susceptible individual becomes infectious depends on the number of infectious individuals with whom the susceptible individual comes into contact. The Poisson probability distribution is used to calculate the probability of infection of a susceptible individual. In a homogeneous mixing model, it is assumed that the daily infectious contact rate is constant. The contact rate, A, is defined as the average number of individuals with whom an infectious individual will make sufficient contact (to pass infection) in one day [24]. Thus AS/N is the average number of encounters per day by an infectious individual resulting in an infection of a susceptible individual, and ASI/N is the average number of infections per day caused by all infectives (N is the population size). The parameter
ASI AI

p=Ym=N
is the average number of infections per susceptible individual per day and is the parameter needed in the Poisson probability distribution. The Poisson distribution gives the probability of n successful encounters resulting in infection of a susceptible person by the infective class in one day [12]: p(n) = ebppn/n!.

Because it takes just one successful encounter to cause an infection, we need to consider only zero encounters or at least one encounter. Therefore, the probability that a susceptible individual does not become infective is given by P(O) = e -p = exp( - AI/N). Initially we assumed that the population mixed homogeneously, A= constant; however, agreement between observed and simulated results was poor. The epidemic continued for a much longer time period, accumulating as many as 13 more cases in 20 days. In addition, it was necessary to assume that many individuals were initially exposed. Therefore, we formulated a nonhomogeneous-mixing model; we assumed that A decreased with time. For many epidemics this may be a reasonable assumption. As the epidemic becomes more severe, individuals are more careful of their social contacts

DISCRETE-TIME MODEL

115

and avoid those individuals known to be infectious and those places where contagious individuals reside. This type of behavior may be even more significant in diseases where behavior modification is a significant preventive strategy (e.g., sexually transmitted diseases). We made the assumption hat A = AS(t), where A is constant. Thus, A decreases with time because S(t), the susceptible class, is a decreasing function of time. Other functional forms for A are also reasonable; however, this is one of the simplest forms that is closely related [via s(t)] to the severity of the epidemic. Rvachev and Longini [24] used a transportation operator to connect individual subgroups; individuals are transported from one subgroup to another and transmit the infection to other subgroups in this manner. Since our model will be applied to a measles epidemic in a university setting, we chose another way to model the subgroup interaction. The n subgroups represent 12- 1 individual dormitory complexes (on-campus population) and an off-campus population. Statistical analysis of the data indicated that residence within a dormitory complex had a significant impact on the course of the epidemic [1_5](most likely because of a common cafeteria), and therefore the subgroups were divided according to dormitory complex (associated with each dormitory complex is one cafeteria). Generally, every day an individual is in contact with each of these subgroups. Each individual of the on-campus population, subgroup i, i = 1,2,. . . , n - 1, contacts other members of his or her own subgroup (subgroup i), members of the on-campus population outside her or his subgroup (subgroups j = 1,2,. . . , II - 1, j # i), and members of the entire university population (subgroups i=1,2 ,.. .,n), with daily contact rates hi, A,, and AU, respectively. Therefore, transmission of the infection is modeled not via a transportation operator but via contact with infectious individuals in any one of three groups. The three groups are nested as follows: Subgroup i is a subset of the campus subgroup c consisting of subgroups j = 1,2,. . . , n - 1, which is a subset of the university subgroup U, which is the set of all subgroups j= 1,2 ,...> IZ. Therefore the parameter p in the Poisson distribution must be replaced by a sum of three parameters, pi + wC + pL,, where

and

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L. J. S. ALLEN,

M. A. JONES, AND C. F. MARTIN

where Ni is the population size of subgroup In our nonhomogeneous-mixing model,

i, i = 1,2,. . . , n, and N = Cy= iNi*

n-1

A, = A,
h,=h,

k=l k

c s,(t),
s,(t).

k=l

For the off-campus subgroup (i = n) it was assumed that /Ji = 0 = pC, because these individuals will not have two sources of contact: within and between dormitories. A particular form for the parameter p (= CLi + /-L,+ pu) was assumed because of the interactions in our population. However, it is easy to generalize /I to other forms. For example, if the n subgroups are not nested but distinct, then /I = C~==IILi. The boundary condition, Ei(O, r + l), is discussed next. The number of exposed individuals at time t + 1 is given by the boundary condition Ei(O,c +l)
=Si(t)[l-exP( -~i-~~-_u)] 7 (1)

where si(t) is the number of susceptible individuals and 1 - exp( - pi - pC - pu) is the probability that a single susceptible individual is exposed. Note that the boundary condition in Equation (1) is specified at time t + 1, not at time f. This assumption is needed to verify time invariance of the population size (see Section 3, Theorem 3.2). The value of E,(O,O) is given by the initial conditions. Some additional boundary conditions are given by A,(O, t) = 0 and Zi(O,f) = 0 (2)

for i=1,2,..., II, since no individual is infective immediately after exposure. The proportion of susceptible individuals in a given population can vary significantly owing to the amount of vaccination coverage [9]. Some individuals remain susceptible even after vaccination owing to vaccine failure. A single dose of live vaccine administered at 1.5 months of age or older, the recommended age for measles vaccine in the United States, is at least 95% effective [lo]. In a fully vaccinated population, the susceptible population may still range from 2% to 5%. In our particular population, it was found that there was a total of 5.8% of the population infected in the dormitory complex where the first case was reported. Since most of these cases were reported before the initiation of the vaccination program, it is reasonable to

DISCRETE-TIME

MODEL

117

assume that the original susceptible population was at least 6%. Therefore, the proportion susceptible for our measles epidemic was assumed to be either 0.06 or 0.07 (in two different simulations). The initial conditions of the population prior to the beginning of a measles epidemic have the form S,(O) = UN,, Ei(T,C) = Ai(T,l) and R,(T,t)=(l-a)& (3c) = li(T,l)

=o,

Pa) P-J)

where 0 < a < 1, and for our population a was assumed to be 0.06 or 0.07. The effects of vaccination are included in the model by considering vaccination data from the measles epidemic. Such a large proportion of students were vaccinated during the measles epidemic (Table 1) that it was assumed that those students who were vaccinated were a random sample of the university population. It was assumed that an individual was vaccinated (1) if that individual had not been recently vaccinated or (2) if that individual had not recently been diagnosed with measles. In addition, it was assumed that vaccine efficacy was 95%. Therefore, the fraction of students vaccinated in subgroup i is given by 0.95Iq f) ~(f)=N,-~(t-i)-TM,(t-l) where Vi(t) is the number of students vaccinated on day t, 1\1;: is the number of students in subgroup i, m(t - 1) is the cumulative number of students

TABLE Percent Vaccinated

in Each Subgroup % Vaccinated 46.7 50.7 39.5 47.0 42.2 50.0 42.5 27.3 54.2 37.9 19.1

Subgroup 1 2 3 4 5 6 7 8 9 10 11

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L. J. S. ALLEN, M. A. JONES, AND C. F. MARTIN

vaccinated by time t - 1, and TMi(t - 1) is the cumulative number of students reported as having measles by time t - 1. If a vaccine is administered within 72 h after exposure, it can still provide protection against measles infection [lo]. Therefore, those individuals exposed and vaccinated within 3 days, Ei(7, t),T = 0,1,2,3, entered the removed class, Ri(t). Implicit in this assumption is that P(T) = 0 for r = 0,1,2,3; individuals cannot become infective within the first 3 days after exposure. The state equations for the model can now be given: si(t+l)=[l-P,(t)][si(t)-Ei(O,t+l)]

Ei(T+l,t

+l)

[l-Pj(t)]Ei(T,t)r
[I-p(T)]&(T,t),

r = 0,1,2,3
T=4,5 ,..., 71-1,

L$(T +l,t

+I)

P(T)Ej(T,t)+[l-~(T)]Ai(T,t),
[I-6(T)]z&(T,t), T=T1+1,...,72-1

T=o,l

,...,Tl

6(T)Ai(Tyt)+[l-Y(T)]i(T,t), zi(T +l,t +I) =

T=o,l

,...,T2

[1-y(T)]Zi(T,t),

T=T2,...,T3-

Ri(t+l)=Ri(t)+

~
7=0

y(T)Zi(T,t)

+pi(t)

S,(t)-Ei(O,t+l)+

~
7=0

Ei(T,t) 1

where i = 1, 2 , . . . , n and P,(t) is defined in Equation (4). Note that the form of P,(t) is not explicitly considered in the analysis of the model and is needed only for comparing the simulated results to the data. Therefore, other expressions for the probability P,(t) can be formulated. The model consists of the state equations, the boundary conditions, Equations (1) and (21, and the initial conditions Si(0), Ei(7, O),Ai(T, O),Zi(7, O),and Ri(0). An epidemic begins when the initial conditions (3) are positive for Ei(T, t), Ai(7, t), or Zi(7, t> for some i and some T. The initial and boundary conditions are nonnegative. We have assumed that &(T, t) and Ai(T, t) are defined for T = 1,2,. . . , T$ Ei(7, t) = 0 for T = TV + 1,. . . , TV, and Ai(7, t)= 0 for 7 = T2 + 1,. . . , T3. 3. ANALYSIS OF THE MODEL

Three mathematically important properties of the state equations will be verified. The first property states that solutions are nonnegative. The

DISCRETE-TIME MODEL

119

second property states that the system is closed, that is, the population size within each subgroup is constant, and therefore the total population is time-invariant. The third property states that all individuals either remain in the susceptible class or enter the removed class. Since the model is of type SIR (more precisely SZGIZR), individuals do not lose their immunity and reenter the susceptible class.
THEOREM 3.I

Solutions to the state equations are nonnegative. Proof: Since Pjpi(t),P(T), S(7), and y(r) satisfy 0 G P,(t) d 1, 0 d p(7) d 1, 0 < 8(r) < 1, and 0 < Y(T) < 1, and the initial conditions are nonnegative, we need only verify that Si( t) - E,(O, t + 1) > 0. The boundary
THEOREM 3.2

condition,

Equation

(l), gives the desired inequality.

The population &(t)+ g

r=O

size is time-invariant, Ei(T,t)+ 2

7=0

that is, 2
7=0

Ai(T,tj+

Zi(T,t)+Ri(t)=Z$,

(5)

where Ni is the constant population

size for subgroup i = 1,2,. . . , n.

Pro05 The subscript i is omitted for convenience. Let X(t) equal the population size at time t. Consider the population size at time t + 1, X(t + l), which is given by Equation (5), where t is replaced by t + 1. We will show that X(t + 1) = X(t). Making the substitutions from the state equations for S, E, A, I, and R, we obtain the following identity for X(t + 1): X(t+l)=[l-P(t)][S(t)-E(O,t+l)]+
7,

c
7=0

[l-P(t)lE(~,t)
71

-1

+ C
r=4 7,-l

[l-/3(7)]E(T,t)+E(O,t+l)+

c
r=O
7,

P(T)E(T,t)

+ -x
7=O

[14(T)]A(T,t)+

A(O,t

+1)+

2
7=0

a(T)A(T,t)

S(t)-

E(O,t +l)+

i
r-0

E(T,t)

1
.

120 Simplification x(t + 1):

L. J. S. ALLEN, M. A. JONES, AND C. F. MARTIN

of the above expression

leads to the following expression

for

7,

X(t+l)=S(t)+
72-l +

c r=o
c
7=0

-1

E(7,t)+

i
7=0

p(T)E(T,f)+P(Tl)E(Tl,f)

A(T,f)+6(72)A(T2,t)+A(O,t+l)

.Foz(T,f, + Y(Tdz(

T3,f)+z(0,t+1)+R(f).

However, the boundary conditions given by Equation (2) for A and Z are zero, and C~&(T)E(T, t) = 0 because P(T) = 0 for T = 0,1,2,3 (it takes an individual longer than 3 days to become infectious). In addition, p(T1)= lengths of the 8(T2) = y(T3) = 1 because T1, T2, and TV are the maximum three states corresponding to E, A, and Z, respectively. After To, i = 1,2,3, time units an individual must reach the next disease state with probability 1. Therefore,

x(f

+l)=S(f)+

2 7=0

E(T,f)+

2 r=O

A(T,f)+

g 7=0

z(T,f)+R(f),

that is, X(t + 1) = X(f).

Longini [20, 211 has shown the existence of a threshold parameter (specified by a combination of model parameters) in the discrete-time, global epidemic model of Rvachev and Longini [24]. If the parameter values in the model lie below the threshold parameter, an epidemic will not occur. Since our boundary conditions, Equation (l), differ from the model in [24], a threshold parameter similar to that given by Rvachev and Longini cannot be defined. However, the third theorem states that the model satisfies a property typical of SIR models [13]; that is, eventually all individuals either remain in the susceptible class or enter the removed class. We assume that P,(f) = 0 for f 2 T; the vaccination program stops after T time units.
THEOREM 3.3

Assume
equations

that P,(t) = 0 for t 2 T. The asymptotic behavior

satisfy

of the

state

Si(a) + Ri(a)

= N,

DISCRETE-TIME MODEL

121

and

Ej(7,W) = Aj(T,W) = Zj(T,W) = 0

for r = 0,1,. . . , r3 and i = 1,2,. . . , n. In addition, if S,(T) > 0, then S,(w) > 0. Pro06

convenience.

In the first part of the proof First we show that the infinite

we omit sum

the

subscript

i for

2 c [A(T,t)+ t=o
r=l

73

z(T,t)l cm.

(6)

Let m. be the number

of infectives

at time 0, that is,

7=1

Let m, be the number of individuals who become infective at time t, t > 0. The total number of infectives at time 1 satisfies

Since 7s is the maximum length of the infective remain infectious at most 7s time units. Therefore,

period, individuals at time rs,

can

In general,

for t > -r3,

Thus the infinite sum in (6) is bounded by ~J~~~rn, and CTxom, < S(O), since new infective individuals come from the susceptible class. Thus inequality (6) is verified. Because inequality (6) holds for all subgroups, it follows that

k=l I=oT=l

e z [z-$(7,t)+zk(T,t)]

<O,

(7)

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L. J. S. ALLEN,

M. A. JONES, AND C. F. MARTIN

In the remainder of the proof t a T, so that P,(t) = 0. Then

the subscripts

are included.

Suppose

Si( t + 1) = Si( t)exp( - pi - p, - pJ. Since Si(t + 1) is nonincreasing and bounded below, Si(m> exists. In addition, we can show that S,(m) > 0 if S,(T) > 0. Substituting the boundary condition (1) into the state equation for Si(t + l), it follows that

Si(t+l)=S,(t)exp

-$ 2
k=l

z
r=l

[Ak(T,t)+zk(T,t)]

1
. equation can be

For the homogeneous-mixing iterated to obtain

model, the above difference

-k

iT ,,=Tk=l

[Ak(T,77)+zk(T,$]

~=l

1
*

(lo)

Because the sums in (6) and (7) are finite, we denote the three sums in Equations (8), (91, and (10) as a;(t) and the finite limits as lim, _,_ aj(t) = Uj for j = 1,2,3, respectively. Then Si(m) = FirSi( T + t + 1) = Si( T)exp( - (or - a, - gs) > 0 model, we have (11)

if S,(T) > 0. For the nonhomogeneous-mixing

Therefore,

Si(m) is bounded

below by expression

(11).

DISCRETE-TIME MODEL

123

Each term in sum (6) must satisfy

lim 2 t--+mr,i Because

[Ai(r,t)+Zi(7,t)]

=O.

Ai and Zi are nonnegative,

it follows that

lim Ai(7, t) = lim Zi(7, t) = 0 t-m t+m for 7=1,2 ,..., 7-s. From the boundary condition (1) we obtain

Ei(O,m) = lim Ei(O, t) = 0. t+m The above limits and state equations z$(T,W) = 0, for 7 = 1,2,. . . , r3. imply that zqm) = ly -q(w)
n

In addition to showing that the population approaches a stationary distribution, we have shown that the susceptible class will never approach zero if S,(T) # 0. If there are susceptible individuals after the vaccination program stops, then there will always be susceptible individuals [Si(m) f 01. However, the proportion remaining in the susceptible class may be very small [S,(m) = 0] owing to the magnitude of the parameters hi, AC, and A, (or Ai, h,, and A,). 4. MODEL SIMULATION

In January through March of 1989 an outbreak of red measles (rubeola) occurred on the campus of Texas Tech University. Data of confirmed cases were collected by the Lubbock City Health Department [l]. A vaccination program was initiated on February 1, 20 days after the first case was reported [l]. There were 198 students infected during the epidemic; 159 of these were students residing on campus (in dormitories). The number of reported cases per day and the cumulative number of cases are graphed in Figure 1. A thorough statistical analysis of the data was performed [2], and it was found that the dormitory within which an individual resided and the vaccination program had a significant effect on the course of the epidemic. It was because of these findings that the population was subdivided according to dormitory complex. A stochastic simulation model similar to the deterministic model was also developed and compared to the data [l]. The simulation results of the stochastic and deterministic models agreed well with the data under the assumption of nonhomogeneous mixing

124

L. J. S. ALLEN,

M. A. JONES,

AND C. F. MARTIN

Days
FIG. 1. Reported number of cases.

[A = AS(t)]. In this section we will discuss the results of the deterministic simulations. In [19] some simulation results of the deterministic model are discussed, with the assumption that the population mixes homogeneously. Several quantities must be estimated prior to simulation of the model; they include the parameters Ai, A,, and A,, the initial conditions, the boundary conditions, and the probability distributions f(r), g(r), h(7), and

DISCRETE-TIME MODEL TABLE 2 Probability Distributions A and B Distribution A 7 f(T) O-8 1.0 9 1.0 10 1.0 (T1) 11 0.0 12 0.0 13 0.0 14 0.0 15 0.0 L?(T) 0.0 0.0 0.0 1.0 1.0 (72) 0.0 0.0 0.0
h(T) k(r)

125

Distribution B

f(7)
1.0 0.67 0.223 (TV) 0.0 0.0 0.0 0.0 0.0

&T(T)
0.0 0.33 0.777 1.0 0.777 0.33 (72) 0.0 0.0

h(T)
0.0 0.0 0.0 0.0 0.223 0.447 0.33 (TV) 0.0

k(T)
0.0 0.0 0.0 0.0 0.0 0.223 0.67 1.0

0.0 0.0 0.0 0.0 0.0 1.0 (73) 0.0 0.0

0.0 0.0 0.0 0.0 0.0 0.0 1.0 1.0

k(7). We make some reasonable assumptions about the contact rates, the initial conditions, and the boundary conditions to reduce the number of quantities to be estimated. We assume that
Ai = ANi,

i=l

,...,n-1

(A, = 0). This assumption reduces the number of contact rate parameters to three: 71, A,, and A,. Values for the probability distributions used in the simulation were chosen on the basis of information contained in [lo] and are given in Table 2. We considered two different sets of values for the probability distributions that differ in the smoothness of the transition between states and in the length of the average infectious period (3 and 3.9 days, respectively). Basically, as the length of the average infectious period (C:=Jg(7) + h(7)]) increases, the values of the estimated contact rates correspondingly decrease. There are 11 subgroups, with the eleventh _subgroup corresponding to the off-campus population. The epidemic began in subgroup 5; therefore, the initial conditions were chosen so that the number exposed in subgroup 5 was &(T~ - 3,O) = 4.0, and all other initial values were given by Equation (3), where a = 0.06 or CI= 0.07. Vaccination began on the 25th day of the simulation (day 20 of the epidemic). The parameters n, A,, and A, were estimated in each of four different simulations. Two cases were considered for each of the probability distributions (A and B) given in Table 2; in one case the proportion initially infected was assumed to be 0.06, and in the other case it was assumed to be 0.07. The parameter values were chosen as those values that provided the best fit of the simulated curve to the cumulative total number of cases, that is, those values that minimized the sum (over the first 80 days of the simulation) of the absolute value of

126

L. J. S. ALLEN, TABLE Parameter Values and Errors 3

M. A. JONES,

AND C. F. MARTIN

for Each of the Simulations Case 3 Distribution a = 0.07 0.0007 0.010 0.0012 786 Case 4 Distribution a = 0.07 0.0004 0.009 0.0008 775

Parameters x A, A Error

Case 1 Distribution a = 0.06 0.0010 0.019 0.0017 789

Case 2 Distribution a = 0.06 0.0006 0.015 0.0012 784

the difference between the cumulative number infected on day t in the simulation and in the reported results [minClTZ(t)TR(tll]. We shall refer to this minimum value as the error. In dormitory complex 8 the fewest number of vaccinations were given (among all dormitory complexes, i = 1, . . . , n, Table 1); therefore, we should expect a relatively high number of cases, but the reverse occurred. Thus, the proportion susceptible was reduced to 0.03 in dormitory 8.

FIG. 2. Simulated

results

(case 1).

20

60

FIG. 3. Simulated

results

(case 2).

20

80

FIG. 4. Simulated

results

(case 3).

L. J. S. ALLEN,

M. A. JONES, AND C. F. MARTIN

40

Days
FIG. 5. Simulated results (case 4).

The specific parameter values that minimized the error and the value of the error are given in Table 3 for each of the four simulations. The cumulative number of cases for the four simulations is graphed against the reported results in Figures 2-5. There was good agreement between the simulated and observed results in each of the subgroups, i = 1,. . . , 11, especially in cases 1 and 2, when the percent susceptible was assumed to be 6%. A comparison of the simulation to the reported results for each subgroup corresponding to day 60 of the epidemic is given in Table 4 for case 2 (Figure 3) and for case 4 (Figure 5). At one time it was hoped that measles could be eliminated from the United States by 1982 [7]. This goal was to be achieved by maintaining high levels of immunity, by close surveillance of the disease, and by applying strict outbreak control measures [7]. However, this goal was never reached. Initially, these methods brought about a decrease in the number of measles cases. In 1983, the number of measles cases was at an all-time low, 1497 reported cases, but in 1988 there were 3411 cases, and in 1989 there were approximately 17,850 cases [8]. It appears that the present level of immu-

DISCRETE-TIME

MODEL TABLE 4 Results Case 2 (simulated) 12.7 5.9 5.5 8.4 75.3 13.3 14.2 9.5 1.5 12.2 38.7 197.2

129

Comparison

Behveen

Simulated

and Reported

at 60 Days for Cases 2 and 4 Case 4 (simulated) 11.7 5.2 5.0 7.6 86.0 12.2 13.4 6.7 1.3 11.4 35.6 196.1

Subgroup

Reported 14 8 9

4 5 6 7 8 9 10 11 Total 78 10 17 7 10 39 198

in many populations is not sufficiently high to prevent an epidemic. Recently, the Immunization Practices Advisory Committee [Ml recommended two doses of measles vaccine for all children, the first dose at 15 months of age and the second when the child is about to enter school at kindergarten or first grade. (Previously, only one vaccination at 15 months of age was recommended.) The level of immunity necessary to prevent an epidemic is often referred to as herd immunity. For our specific population we can estimate the level of herd immunity by performing the simulations without any vaccinations and increasing the level of immunity until the total number of measles cases is very close to the initial number of infectious individuals (indicating that there were very few new cases of measles). Using the same initial conditions and the estimated parameter values, we simulated each of the four cases without vaccinations and with an increasing immunity rate (up to 99%). The initial assumption was that there were four infective individuals; therefore, herd immunity is achieved if the cumulative number of cases at 80 days is very close to 4. The results of the simulations for the four different cases at various immunity rates is summarized in Table 5. An immunity rate of 99% resulted in approximately a total of one more case of measles. This one case represents a cumulative total over a period of 80 days; therefore, on any one day the number of new cases of measles is much less than 1. Hence, the simulations indicate that an immunity rate in excess of 98% may be required before herd immunity is achieved in a university population. This estimate agrees with the statistical analysis and the simulation results of the stochastic model [l, 21. A level of immunity greater than 98% may be nity

130

L. J. S. ALLEN, TABLE 5

M. A. JONES,

AND C. F. MARTIN

Total Number of Measles Cases at Various Immunity (No Vaccinations Given During the Epidemic) Immunity 94% 95% 96% 97% 98% 99% rate Case 1 393 271 159 68 21 5.5 Case 2 388 265 154 64 18 5.0 Case 3 313 199 103 43 15 5.0

Rates

Case 4 305 193 98 38 11 4.6

impossible to achieve with only one does of measles vaccine because the vaccine may be only 95% effective. Therefore, requiring two measles vaccinations may increase the level of immunity in the population so that herd immunity is achieved. 5. CONCLUSION

A general discrete-time SIR-type model with vaccination was formulated, analyzed, and applied to data of a measles epidemic on a university campus. It was assumed that the contact rate A was not constant but decreased with time, that is, A = AS(t) (nonhomogeneous-mixing population). The model simulations for the nonhomogeneous-mixing model were found to agree much better with data than those for the homogeneous-mixing model. An estimate of the !evel of herd immunity required to prevent an epidemic in a university population was estimated ( > 98%). The estimate agreed with estimates derived from a statistical analysis of data and a stochastic simulation. Additional tests and simulations using data from other comparable epidemics are required to substantiate some of the assumptions and the estimates derived from simulations of this particular epidemic. The general model has applications to other contagious diseases of SIR type, such as chickenpox, mumps, or rubella, where data can be compared to simulated output. The effects of various vaccination strategies can also be compared.

REFEREYCCS 1 2 L. Allen, simulation T. Lewis, C. F. Martin, and M. Stamp, A mathematical analysis and of a localized measles epidemic, Appl. Math. Camp. 39:61-77 (1990).

L. Allen, T. Lewis, G. Mundel, C. Martin, A. Way, C. K. Lo, and M. Stamp, Analysis of a measles outbreak (submitted for publication).

DISCRETE-TIME 3 4 5 6 7 8 9 10 11 R. M. Anderson

MODEL and R. M. May, Directly transmitted infectious diseases: control

131
by Nov.

vaccination, Science 215:1053-1060 (1982). R. M. Anderson and R. M. May, The logic of vaccination,

New Sci. 96:410-415,

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H. W. Hethcote, Optimal ages of vaccination for measles, Math. Biosci. 89:29-52 (1988). H. W. Hethcote and P. Waltman, Optimal vaccination schedules in a deterministic epidemic model, Math. Biosci. 18:365-381 (1973). H. W. Hethcote and J. W. Van Ark, Epidemiological models for heterogeneous populations: proportionate mixing, parameter estimation, and immunization programs, Math. Biosci. 84:85-118 (1987). Immunization Practices Advisory Committee, Measles prevention: recommendations of the Immunization Practices Advisory Committee, Morb. Mortal. wkly. Rep. 38, no. S-9 (1989). M. A. Jones, A. deterministic mathematical model of a measles epidemic, Masters Report, Texas Tech University, Lubbock, Tex., 1990. I. M. Longini, Jr., The generalized discrete-time epidemic model with immunity: a synthesis, Math. Biosci. 82:19-41 (1986). I. M. Longini, Jr., A mathematical model for predicting the geographic spread of new infectious agents, Math. Biosci. 90:367-383 (1988). A. R. McLean and R. M. Anderson, Measles in developing countries. Part II. The predicted impact of mass vaccination, Epidemiol. Infect. 100:419-442 (1988). R. M. May, Vaccination programmes and herd immunity, Nature 300:481-483 (1982). A. L. Rvachev and I. M. Longini, Jr., A mathematical model for the global spread of influenza, Math. Biosci. 75:3-22 (1985). D. W. Tudor, An age-dependent epidemic model with application to measles, Math. Eiosci. 73:131-147 (1984).

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