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A detailed probabilistic treatment is given of a birth-and-death process proposed by Williams (1969) in which the elements of the process bear up to s inanimate marks. Equations for the second-order moments of the process, and approximate marginal univariate solutions, are derived. The exact bivariate solution is given for the case s = 1. For general s the variance of the mark population is also derived. MARKED BIRTH-AND-DEATH PROCESS; MULTIVARIATE LAGRANGE DIFFERENTIAL EQUATIONS; MULTITYPE BRANCHING PROCESS Introduction In a recent paper Williams (1969) has considered the following process. We have a population of elements developing as a linear birth-and-death process and each element bears a number of inanimate marks. When a marked element dies then it and its marks are removed from the population; when a marked element divides, its marks segregate independently and without loss, each with probability I into one of the two daughter elements. It is assumed that marking an element does not affect its birth and death rates (cf. Clifford and Sudbury (1972)). Williams' process was proposed as a model of an experiment conducted on bacteria (the elements) infected by phage (the inanimate marks), by Meynell (1959). (The bacteria are lysogenic with respect to the phage, which means that the phage do not interfere with the behaviour of the bacteria.) His object was to use the marking process in order to separate the birth and death rates of the bacteria; if we denote birth and death rates by A and p respectively, then the mean-value measures on the bacterial population (assumed to develop as a linear birth-and-death process) will estimate the difference (A p). As the marks are inanimate, however, they will only be affected by p and so mean-value measures on the mark population enable us to estimate p (see Williams (1969)). The papers of Meynell and Williams taken together provide a most interesting example of a virological experiment and the probability model of that experiment. Received in revised form 10 August 1973 Research sponsored by a Science Research Council grant and a World Health Organisation research traineeship. 423 This content downloaded from 207.46.13.180 on Thu, 08 Sep 2016 05:01:40 UTC All use subject to http://about.jstor.org/terms 424 BYRON J. T. MORGAN Williams considered the mean-value solution of his model; this was adequate for Meynell's experiment in which population sizes were large. Here we shall give a fuller probabilistic statement of the model and make some contributions to its solution. Two differences from Williams' work lie in the adoption of an upper bound, s, to the number of marks any element can have, and the assumption (except where stated) of birth and death rates independent of time. We 'shall assume general initial conditions which, in Meynell's experiment, correspond to the distribution of phage over bacteria once these have been initially exposed to a phage population. Williams took this distribution to be Poisson; the distribution of phage over bacteria has, however, been the subject of much probabilistic study (e.g., see Gani (1965) and Morgan (1971)). Finally, let us note that the value s = I, on which we shall particularly concentrate, probably gives the most realistic description of Meynell's experiment. 2. The probability model The model is a continuous-time Markov process with discrete states. Let N,(t) be a random variable denoting the number of elements with i marks at time t, i = 0, 1,2, ..., s. Let n = (n0,n1, l , n.., ), Iu = (Uo, u1, *,us), N(t) = (No(t), N(t), --,N,(t)), and suppose N,(O) = ai, i = 0, 1,2, --, s. Let P(n; t) = P(N(t) = n), then corresponding to death we have the transitions, (No, ..., Ni, ---, N,) (No, --, Ni 1, , N,) at probability rate pNi, i = 0, 1,2, ,s, while corresponding to birth we have the following transitions (No, N,) ,(No + 1, .., N,) at probability rate, 2 =1 N 2-' +,ANo, (No, , Ni ,N2i,..., X (No, Ni + 2, , N2iI, at probability rate, This content downloaded from 207.46.13.180 on Thu, 08 Sep 2016 05:01:40 UTC All use subject to http://about.jstor.org/terms On the distribution of inanimate marks over a linear birth-and-death process 425 where we use [is] to denote the integral part of is, and (No, " , Ni, * * *, Nk i Nk, "', Ns) -*(No, ..., Nj + 1, ..., Nk-i + 1, ..., Nj 1, ..., Nl) at probability rate 2N 2-k' i = 1,2,...,C[(k 1)], k = 3,4,...,s (smaller k give transitions already considered above). It is readily verified that the sum of the transition rates is (A + yp) X = oN,, as required in the overall birth-and-death process. Introducing the operator Di, which increases the argument ni of a function of n by 1, we then deduce that the Kolmogorov forward equations (for all possible n) are, d S S (1) +(n; t) P(n; t)(A+ t)1 (n2 + D,P(n;t)(n +1) dt ==0 1=0

This paper applies the constant population approximation to the study of epidemics which involve more than a single type of infective. An example of this would be a situation in which both clinically infected individuals and subclinically infected individuals or carriers are present. We derive equations for the expected numbers of clinically infected individuals and carriers at any time t for the model with zero latent period and infectious periods having negative exponential distributions. From these equations we derive conditions under which a unimodal incidence curve can result, and expressions for the expected total epidemic size. The equations describing the course of an epidemic are analytically intractable except in certain simple cases, [1]. When one examines the reason for the mathematical difficulties that arise, one finds that the principal stumbling block is the assumption of a finite population of susceptibles. It can be argued, however, that in modern societies epidemics very rarely menace an entire population, and that observed epidemic sizes are usually much smaller than the total susceptible population. This is due to a variety of reasons, among which are public health measures and good communication facilities available to a modern society. In consequence it is reasonable to try to bypass some of the mathematical difficulties inherent in the theory of epidemics by assuming a susceptible population whose size does not change through the course of the epidemic. Bailey [2], Morgan [3], and Williams [4] have discussed in some detail the theory of epidemics using the constant population approximation, although such an approximation was used by several authors earlier, [5], [6], [7]. The theory developed so far has dealt mainly with epidemic processes in which there is only a single type of infective and a single type of susceptible. Recently Gart [8] has considered a model for epidemics involving more than one type of susceptible. It is the purpose of this paper to analyze the development in time of epidemics which involve more than a single type of infective individual. This Received in revised form 3 January 1967. 257 This content downloaded from 157.55.39.78 on Mon, 20 Jun 2016 07:20:57 UTC All use subject to http://about.jstor.org/terms 258 HUGH M. PETTIGREW AND GEORGE H. WEISS problem, in which there may be several types of infectives, is suggested by diseases in which carriers are important, [9]. In the present paper we derive equations for the expected numbers of carriers and clinically infected individuals at any time t, in the case of a zero latent period and negative exponential distributions of infectious periods. From these equations we will give the conditions under which an epidemic arises from the introduction of a bearer of the disease, i.e., the conditions under which the reporting curve increases initially. These conditions are of some theoretical interest since Bailey has shown that in the infinite population approximation to an epidemic with only one class of susceptibles and one class of infected individuals, no initial increase in the reporting curve can occur. Finally, we derive expressions; for the expected total epidemic size. Let us consider a homogeneously mixing population which, in the present approximation, can be characterized by four parameters, yi(t), y,(t), zi(t), zc(t). These are, respectively, the number of clinically infected individuals, the number of carriers, the cumulative number of removals of infectives, and the cumulative number of removals of carriers, all evaluated at time t. The probability that a single susceptible individual will become clinically infected in (t, t + dt) is assumed to be fli(y, + yc)dt, and the probability that a susceptible will become a carrier is assumed to be Ic(yi + ye)dt, where both l's are assumed to be constant and it is assumed for simplicity that carriers and infectives are equally infectious. The constancy of these p's is the principal assumption of the present theory; in the more detailed stochastic theory discussed by Bailey [1] the f's are proportional to the number of susceptibles as well. In the simplest model, we assume that the latent period is zero, i.e., that newly infected individuals are immediately capable of infecting others, and that the infectious period is a random variable with a negative exponential distribution. The rate parameter appearing in the distribution for clinically infected will be denoted by vi and that appearing in the distribution for carriers will be denoted by v,. In order to describe the stochastic process we introduce a set of probabilities p(r,,r2, r3, r4, t) defined by p(r, t) = Pr{y,(t) = r, yc(t) = r2, z(t) = r3, zc(t) = r4}. By our assumptions the p(r, t) satisfy ap = fl (r1 + r2 1)p(r, 1,r2,r3, r4, t) + fl(r, + r2 -1)p(r1,r2 1,r3, r4, t) (1) + vA(r1 + 1)p(r + 1,r2, r 1,r4)+ vc(r2 + 1)p(r, r2 + 1, r3,r4 1) [(fl + ic + vi)rl + (fl + flPc + ve)r2] p(r, t). This content downloaded from 157.55.39.78 on Mon, 20 Jun 2016 07:20:57 UTC All use subject to http://about.jstor.org/terms Epidemics with carriers: the large population approximation 259 The moment generating function (2) M(01, 02, 03 , 0,t) = M(O, t) = E{eo'Y'+2yYc+03zi+042C} therefore satisfies aM M = [f#,(ee I1) + flc(e02 1) + vi(ee, +03 1)] (3) aM + [fl(ee' 1) + flc(e02 1) + vc(e-02+4 1)] The interesting features of the development of the epidemic can be determined by analyzing the properties of the mean values Lpi(t) = E{yi(t)}, pc(t) = E{yc(t)} (4) ow(t) = E{z,(t)}, wc(t) = E{zc(t)}. The equations for these mean values are easily determined by equating coefficients of the O's on both sides of Equation (3). They are Pi = (/01v-i)it?+fliltc (5) Pc = flcpi+ (fc v)Pc

Distributions of some random variables have been characterized by independence of certain functions of these random variables. For example, let X and Y be two independent and identically distributed random variables having the gamma distribution. Laha showed that U = X + Y and V = X | Y are also independent random variables. Lukacs showed that U and V are independently distributed if, and only if, X and Y have the gamma distribution. Ferguson characterized the exponential distribution in terms of the independence of X – Y and min (X, Y). The best-known of these characterizations is that first proved by Kac which states that if random variables X and Y are independent, then X + Y and X – Y are independent if, and only if, X and Y are jointly Gaussian with the same variance. In this paper, Kac's hypotheses have been somewhat modified. In so doing, we obtain a larger class of distributions which we shall call class λ1. A subclass λ0 of λ1 enjoys many nice properties of the Gaussian distribution, in particular, in non-linear filtering.