<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">NS</journal-id><journal-title-group><journal-title>Natural Science</journal-title></journal-title-group><issn pub-type="epub">2150-4091</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/ns.2012.48075</article-id><article-id pub-id-type="publisher-id">NS-21997</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biomedical&amp;Life Sciences</subject><subject> Chemistry&amp;Materials Science</subject><subject> Earth&amp;Environmental Sciences</subject><subject> Medicine&amp;Healthcare</subject><subject> Physics&amp;Mathematics</subject></subj-group></article-categories><title-group><article-title>
 
 
  Time delay in non-lethal infectious diseases
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>.</surname><given-names>De Luca</given-names></name><xref ref-type="aff" rid="aff1"><sub>1</sub></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Dipartimento di Fisica “E. R. Caianiello”, Università degli Studi di Salerno, Fisciano, Italy</addr-line></aff><author-notes><corresp id="cor1">* E-mail:<email>rdeluca@unisa.it</email></corresp></author-notes><pub-date pub-type="epub"><day>29</day><month>08</month><year>2012</year></pub-date><volume>04</volume><issue>08</issue><fpage>562</fpage><lpage>568</lpage><history><date date-type="received"><day>27</day>	<month>March</month>	<year>2012</year></date><date date-type="rev-recd"><day>30</day>	<month>April</month>	<year>2012</year>	</date><date date-type="accepted"><day>13</day>	<month>May</month>	<year>2012</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
  The effects of the incubation period q on the dynamics of non-lethal infectious diseases in a fixed-size population are studied by means of a delay differential equation model. It is noted that the ratio between the quantity q and the time τ for recovering from the illness plays an important role in the onset of the epidemic breakthrough. An approximate analytic expression for the solution of the delay differential equation governing the dynamics of the system is proposed and a comparison is made with the classical SEIR model.
 
</p></abstract><kwd-group><kwd>Delay Differential Equations; Infectious Diseases</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. INTRODUCTION</title><p>The dynamics of infectious diseases in a closed population is a well known topic in the literature [1-5]. These models are commonly classified using the prefixes SIR and SEIR. In the first type of models susceptible (S), infectious (I) and recovered (R) individuals are considered; in the second, the exposed (E) class of individuals is also taken in account. By denoting as<img src="7-8301637\4de32fa5-c6f4-421d-86f1-b69f30b740f6.jpg" />, <img src="7-8301637\68699588-73e8-4406-8d17-932101b01a7f.jpg" />and <img src="7-8301637\19bfde19-5e79-4104-a9c4-1801c1e96617.jpg" /> the number of individuals belonging to the class S, I, and R, respectively, at time t, the basic SIR model can be resumed in the following three differential equations [<xref ref-type="bibr" rid="scirp.21997-ref6">6</xref>]:</p><disp-formula id="scirp.21997-formula138978"><label>, (1)</label><graphic position="anchor" xlink:href="7-8301637\637d1832-ac93-4737-9035-710ba93babd8.jpg"  xlink:type="simple"/></disp-formula><p>where the dot represents derivative with respect to time and <img src="7-8301637\091dc1ed-ad4b-4c00-81c7-34a5080aad5a.jpg" /> is the total number of individuals in a fixed-sized community and where the parameters are β and γ are the effective infection rate and the recovery rate, respectively. The above set of differential equations can be reduced to two by means of the definition of N given above. Here an exponential distribution of the recovery time is assumed, so that the quantity 1/γ corresponds to the average period which a single individual spends to recover from the illness. Adopting the above description of the time evolution of the number of individuals belonging to the three classes, one can see that an equilibrium point appears in the system if <img src="7-8301637\098cc752-5b77-4611-9b91-55dc039ba674.jpg" />. In the classical SIR model <img src="7-8301637\d3df9ddf-31f3-4491-924a-1c8e300a6edd.jpg" /> is the basic reproduction number, which accounts for the average number of successful contacts an infectious individual has with a susceptible one at the first appearance of the illness in the community.</p><p>On the other hand, a SEIR model can be represented by the following set of equations [<xref ref-type="bibr" rid="scirp.21997-ref6">6</xref>]:</p><disp-formula id="scirp.21997-formula138979"><label>, (2)</label><graphic position="anchor" xlink:href="7-8301637\3433068d-f36a-44d2-94ab-187c920c24ae.jpg"  xlink:type="simple"/></disp-formula><p>where the exposed (E) class of individuals, whose number at time t is<img src="7-8301637\88136aae-71d7-413c-ae7b-f10efe94de8e.jpg" />, is added. In this way, assuming an exponential distribution of the quiescent period the inverse of the additional parameter ε represents the average quiescence time of the illness. Notice, finally, that the total number of individuals is now given by <img src="7-8301637\ed4fe2f6-f7db-4438-b646-5c3b2c93009b.jpg" />.</p><p>We may notice the nonlinear prey-predator interaction in the first two terms of the above set of equations. The same mass action term is taken to represent the process of infection of the susceptible (S) and the infectious (I) class of individuals in the semi-continuous time delay model by Noviello-Romeo-De Luca (NRD) [<xref ref-type="bibr" rid="scirp.21997-ref7">7</xref>]. In the latter model only one non-linear delay differential equation (DDE) is needed, namely:</p><disp-formula id="scirp.21997-formula138980"><label>, (3)</label><graphic position="anchor" xlink:href="7-8301637\3ed3f1cb-0ae5-4a97-8e38-469d40e8feae.jpg"  xlink:type="simple"/></disp-formula><p>where <img src="7-8301637\014ddb64-5798-4782-b0ca-3532a0aa1ab4.jpg" /> is the count of all illness histories up to time t, starting from t = 0, p is the effective statistical exchange parameter between classes S and I, <img src="7-8301637\3c7152e2-85ed-489d-9d68-ea5a7c753a06.jpg" />, and τ &#160;is the average recovery time. The number of individuals belonging to the S, I and R classes can be found by the following elementary relations:</p><disp-formula id="scirp.21997-formula138981"><label>, (4a)</label><graphic position="anchor" xlink:href="7-8301637\866b9906-948b-41b2-b85c-0c4c855a9f4c.jpg"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.21997-formula138982"><label>, (4b)</label><graphic position="anchor" xlink:href="7-8301637\59d41744-4235-4d87-881c-9d675acc9162.jpg"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.21997-formula138983"><label>. (4c)</label><graphic position="anchor" xlink:href="7-8301637\6da55af2-c7aa-4685-bc20-fbc2cb7014aa.jpg"  xlink:type="simple"/></disp-formula><p>In the present work we extend the NRD model to the case in which a constant quiescence time q is introduced. The effects on the dynamics of the two time-delays τ and q are studied and an approximate solution for the extended NRD model is proposed. A comparison between the classical SEIR model and the extended NRD model is also made.</p></sec><sec id="s2"><title>2. THE EXTENDED NRD MODEL</title><p>A detailed treatment of the NRD model can be found in ref. [<xref ref-type="bibr" rid="scirp.21997-ref7">7</xref>]. Starting from a semi-continuous approach, it has been shown that a single globally continuous function <img src="7-8301637\5c77e25d-2692-4dcf-8493-ebb376b62eb0.jpg" /> can be adopted to describe the dynamics of all classes of individuals, namely S, I, and R. This model gives good qualitative agreement with existing data on influenza. The recovery time τ in the NRD model is seen to represent a natural time scale and appears as a constant delay time in the nonlinear differential eq.3. Starting now from Eqs.4a-c, in the presence of the additional E-class, we can write:</p><disp-formula id="scirp.21997-formula138984"><label>, (5a)</label><graphic position="anchor" xlink:href="7-8301637\6c1b460a-d78a-4bc0-bfb9-fc3d16ce2ebd.jpg"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.21997-formula138985"><label>, (5b)</label><graphic position="anchor" xlink:href="7-8301637\569242ae-1db7-4557-b965-e23405bbc6bf.jpg"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.21997-formula138986"><label>, (5c)</label><graphic position="anchor" xlink:href="7-8301637\4047d485-fc9c-4790-9db7-62c90443aab4.jpg"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.21997-formula138987"><label>, (5d)</label><graphic position="anchor" xlink:href="7-8301637\92b5da0e-18ab-4c61-bf65-09e40e788799.jpg"  xlink:type="simple"/></disp-formula><p>This type of generalization is done by noticing that individuals who have been exposed at time <img src="7-8301637\fbf4deb4-226c-47e8-a985-db970e47e053.jpg" /> get ill at time t, while those being infected at time<img src="7-8301637\70dfae44-b10b-442d-90c2-e6286d9431d8.jpg" />, recover at time t. The dynamical equation can thus be written as follows:</p><disp-formula id="scirp.21997-formula138988"><label>. (6)</label><graphic position="anchor" xlink:href="7-8301637\eaa8b19f-92a6-4501-a652-3b5f6c4060e2.jpg"  xlink:type="simple"/></disp-formula><p>Therefore, in this extended model a second delay time naturally arises and the effective interaction between individuals belonging to the S and I class is modified because of a different expression for <img src="7-8301637\915f154c-e417-4f69-9eba-67bb5fe730c4.jpg" /> in Eq.5c. Consider q &lt; τ for simplicity, and assume that, at time –q, exactly <img src="7-8301637\42416caf-7621-48ed-bcc8-48f7f8909bd0.jpg" /> individuals are exposed to infective agents. Therefore, for t &lt; 0, we have<img src="7-8301637\956ab263-f584-4658-9555-eb8d52cac9fe.jpg" />, <img src="7-8301637\6963459d-eeaf-49bc-80d9-dd943e8ad64a.jpg" />, and</p><disp-formula id="scirp.21997-formula138989"><label>, (7a)</label><graphic position="anchor" xlink:href="7-8301637\d8f2e727-0113-4579-965d-62c6804ffdb4.jpg"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.21997-formula138990"><label>. (7b)</label><graphic position="anchor" xlink:href="7-8301637\c492f5c7-4a0f-4742-8a2d-648926f403d2.jpg"  xlink:type="simple"/></disp-formula><p>In this way, we have</p><disp-formula id="scirp.21997-formula138991"><label>. (8)</label><graphic position="anchor" xlink:href="7-8301637\1c2a0456-771a-40fc-8be6-8cf87066d936.jpg"  xlink:type="simple"/></disp-formula><p>The above relation is needed in specifying the past history of the system, whose dynamics is described by the DDE in Eq.6.</p><p>We may notice that the extended NRD model can find application for all those maladies whose characteristics call for well-defined incubation and recovery periods for all individuals in the community. We shall therefore see in details, in the following sections, all peculiar features of the model. We finally notice that the NRD model can be simply obtained from the extended NRD model in the limit q = 0.</p></sec><sec id="s3"><title>3. CHARACTERISTIC FEATURES OF THE MODEL</title><p>We have seen, in the preceding section, that the NRD model and its extended version rely upon a single timedelay differential equation, namely, Eq.6. When expressing this equation in terms of the rescaled time variable <img src="7-8301637\fda0f4f1-37ef-4655-911f-fcd30a45301d.jpg" /> and of fractional quantities <img src="7-8301637\0b5ec22c-35c9-42a7-87b2-a6264299d18d.jpg" />, by defining<img src="7-8301637\b3e85f82-f495-46ed-a443-bdd6f0d643a9.jpg" />, we may write:</p><disp-formula id="scirp.21997-formula138992"><label>. (9)</label><graphic position="anchor" xlink:href="7-8301637\abc0ad5c-4660-496e-a581-34bf378ba37f.jpg"  xlink:type="simple"/></disp-formula><p>By defining<img src="7-8301637\6670d6a2-cccc-4fd1-8219-e50ac19d710f.jpg" />, we notice that the above differential equation can be described in terms of the normalized variable <img src="7-8301637\4c6d869a-77e8-454c-aef3-b3196477b6ca.jpg" /> of the count of individuals who got ill from the beginning of the epidemic onset, by considering the delay ratio r, the initial value of infectious individuals m<sub>0</sub> and <img src="7-8301637\50a43382-6cac-469d-8dfc-c2d1f40bb89b.jpg" /> as the constant parameters of the scalar model in Eq.9. Notice that the quantity<img src="7-8301637\ceed3dcd-e9c1-4506-91e9-40f026cde3c6.jpg" />, by definition, plays the same role as the&#160; basic reproduction number R<sub>0</sub> in the classical SIR and SEIR models.</p><p>In the present work we would like to study the effect of the introduction of the delay ratio r in the DDE (9). At first let us then consider the time dependence of the percentage of infectious individuals obtained by fixing the values of m<sub>0</sub> and<img src="7-8301637\43af9a34-a4f7-46ee-82fd-bd7fca34e002.jpg" />. In figures 1(a), (b), therefore, we show the numerical solution to Eq.9 for <img src="7-8301637\0bc8290f-e012-45b3-99bc-0296fd564f71.jpg" /> and <img src="7-8301637\86aa916a-3dd5-4493-bfd8-3b96136c4c21.jpg" /> and for various values of r. In these curves we notice that, by increasing r from the very low value of 0.01 to 0.5, the total number of individuals <img src="7-8301637\eea2c736-384d-4f62-bedf-2bf6650c3ead.jpg" /> infected during the epidemic outbreak decreases.</p><p>This property is represented in figure 2, where the fraction <img src="7-8301637\303e6947-adf5-4d73-a993-7f5d699141b9.jpg" /> is reported as a function of r, the line joining the numerically determined points being a</p><p>guide to the eye. Therefore, one might argue that increasing incubation periods give a minor spread of the disease among the global population. In figures 3(a), (b) we report the time dependence of the fraction <img src="7-8301637\691d2d23-efbf-4eba-bea9-1db1e685cf8c.jpg" /> of infected individuals for the same values of parameters as in figures 1(a), (b). The characteristic hump of these curves gets lower and shifts to the right for increasing values of r. In figures 4(a), (b) the onset of the epidemic outbreak can be detected in the curves of the fraction <img src="7-8301637\0f052dfd-1bdb-417d-afa7-f74d23299995.jpg" /> as a function of<img src="7-8301637\7109a0dc-5cf8-4177-b978-a86a6727cb9a.jpg" />.</p><p>&#160; One notices that, below a certain value of<img src="7-8301637\b7b2a183-0976-438a-bbf4-8098f662ec61.jpg" />, which</p><p>we denote by<img src="7-8301637\0bb973a3-f1e5-42fb-8f0a-13a3c0f4e0dd.jpg" />, the disease is not able to spread significantly among the susceptible individuals, as it happens in the classical SIR and SEIR models. As it appears from figures 4(a), (b), the value of <img src="7-8301637\52273830-c187-40ce-8256-82487d1fff25.jpg" /> is expected to be higher for increasing values of r. Indeed, by collecting points of various critical effective interaction parameter <img src="7-8301637\f281f199-c977-4877-8210-017cab706a61.jpg" /> for various values of the delay ratio r, we may represent the <img src="7-8301637\cfb8f5a2-c14b-4c91-90e3-766452d84276.jpg" /> vs. r curve for <img src="7-8301637\2aab9a75-0bfd-4597-ade7-6de2f6fc98ab.jpg" /> of figure 5. In this plot all points are obtained by defining the onset of the disease in the <img src="7-8301637\4710de36-40b0-4035-be05-98786e240890.jpg" /> vs. <img src="7-8301637\385c1aa3-073c-407a-8511-e5720e337ed6.jpg" />curves as the value of <img src="7-8301637\29c5331f-f481-446f-9f40-d283e68d937a.jpg" /> for which<img src="7-8301637\d4aa91e3-af5f-420f-8376-d551bdda8b44.jpg" />. The continuous line is the result of interpolation of the points in the plot, numerically obtained from the <img src="7-8301637\92ad504c-e130-4866-945d-503fb77e883f.jpg" /> vs. <img src="7-8301637\e34481fb-03df-4af4-a03e-ac0275a665b5.jpg" />curves, with a trial function<img src="7-8301637\4b393a09-b544-4b5b-8273-6f28dbc248fe.jpg" />, with<img src="7-8301637\fc8cc60e-3ced-4a65-835b-65bf691c602c.jpg" />. This simple mathematical relation can be understood in the following way. Assuming an increasing behavior for<img src="7-8301637\26ce47cc-73ca-4c7d-94b2-f4357906d34e.jpg" />, let us write, for reasons which will be apparent in the following section, <img src="7-8301637\17817c08-e1bb-4e12-9d4a-9895c8f72a93.jpg" />in the limiting region <img src="7-8301637\df54eec3-3eba-4b27-8682-bf98d84259ab.jpg" />, with b arbitrary constant and<img src="7-8301637\11ecf3c4-b4c7-4a54-809c-04a9ffe0b0f8.jpg" />.</p><p>Assuming an increasing behavior for<img src="7-8301637\9aea0750-d20e-4791-8cbf-b749c8ed95f8.jpg" />, let us write, for reasons which will be apparent in the following section, <img src="7-8301637\24e18db5-0784-4730-8415-d65db79574b3.jpg" />in the limiting region</p><p><img src="7-8301637\7d557a45-7445-4d50-a2cf-26e7a8fce989.jpg" />, with b arbitrary constant and<img src="7-8301637\e31c9100-84a9-47ec-8478-eddc1b1c4e73.jpg" />. By taking the derivative with respect to <img src="7-8301637\d5ae1fb9-4fed-44bf-8eeb-dfd3389eda77.jpg" /> and substituting this expression in Eq.10, one finds, to first order in <img src="7-8301637\a847b5c8-446a-464c-b695-45a55a022631.jpg" /> and</p><p>leading order in <img src="7-8301637\cc72c271-1104-4012-80aa-e2c8de6c0000.jpg" /> a simple expression, expressed term by term as follows</p><disp-formula id="scirp.21997-formula138993"><label>. (10)</label><graphic position="anchor" xlink:href="7-8301637\3ebb7392-2cd4-44f8-8ad7-598ea39a2690.jpg"  xlink:type="simple"/></disp-formula><p>In this way, after obvious simplifications, we have:</p><disp-formula id="scirp.21997-formula138994"><label>, (11)</label><graphic position="anchor" xlink:href="7-8301637\dc91c3d3-1772-4074-a6ed-43ade9782bc7.jpg"  xlink:type="simple"/></disp-formula><p>where</p><disp-formula id="scirp.21997-formula138995"><label>. (12)</label><graphic position="anchor" xlink:href="7-8301637\219b18c8-7ee6-4a38-9329-5dd4b173c9e9.jpg"  xlink:type="simple"/></disp-formula><p>We thus obtain, by this approximate relation, further evidence that the threshold of the infectiveness parameter <img src="7-8301637\b55d1edf-68d5-453a-be7f-eea68532fda7.jpg" /> increases as r increases as described by the numerical results shown in figure 5.</p><p>We can now make a comparison between the dynamics obtained in the extended NRD model and the classical SEIR model. We have already specified that the quantity <img src="7-8301637\40a08191-b1a7-4101-8a0c-330800bf7d0a.jpg" /> plays the same role as the basic reproduction number R<sub>0</sub> in the SIR and SEIR models, Eq.12 giving an approximate evaluation of the threshold infectiveness parameter value for the extended NRD model. In the classical SEIR model, on the other hand, the inverse rates <img src="7-8301637\4b33bb75-e410-48bf-a52f-c71f71a4dfb4.jpg" /> and <img src="7-8301637\85da035b-57d5-43de-8f1a-352c3009b8a5.jpg" /> corresponds to the average times which a single individual spends in the E or I class, the statistical spread being exponential. The classical SEIR model and the extended NRD model are thus expected to be of different analytical nature, the latter calling for well defined recovery time τ and incubation period q. As an example one can detect this difference in the time dependence of <img src="7-8301637\859dfdaa-a0c4-4145-bab0-e2568315baa0.jpg" /> curves for both models by setting <img src="7-8301637\be4aef9e-ee26-4d62-ab6b-f7d3f9baf21f.jpg" /> and<img src="7-8301637\d85fa327-7c25-46ef-808d-c5619f828dbc.jpg" />, so that<img src="7-8301637\55b97ec1-03ed-4aa1-b7a7-d25f6ffc77d9.jpg" />, adopting the same values of the parameters <img src="7-8301637\39a8eb95-d6d3-4777-817a-d8e65fc2bf1e.jpg" /> and <img src="7-8301637\1d34d3af-83b3-4b65-8773-f497ff022f1b.jpg" /> and making the correspondence <img src="7-8301637\3b0c02f3-1281-46fa-ba59-828e832f14bb.jpg" /> for the two models.</p><p>This comparison is very instructive, since it gives a hint on the type of approximation one can make to describe the behaviour of the solution in the asymptotic region, as it has already been done in writing Eq.10. Therefore, in figures 6(a) and (b) we show <img src="7-8301637\b779701e-8e10-40fb-a947-cd59bd482e33.jpg" /> curves for the classical SEIR model and the extended NRD model, respectively, for the following values of the delay ratio r: 0.01; 0.1; 0.2; 0.3; 0.4. First of all, we may notice the different pattern in the rise and fall in time of the groups of curves in figure 6(a) and in figure 6(b). This difference and the approximately symmetric pattern about the peak values of the curves in figure 6(b) allow a Gaussian-type approximation of the <img src="7-8301637\9cd74016-59b2-4694-996f-84632dcc5c35.jpg" /> curves obtained for the extended NRD model, as we shall see in the following section. Furthermore, one may also notice a more pronounced decrease of the peak values of the <img src="7-8301637\f01e3b86-329f-4355-b7bf-1b39058d5afb.jpg" /> curves on increasing the delay ratio r in the extended NRD model, as compared to a correspondingly equal increase of the ratio <img src="7-8301637\66c59de0-3ffe-4bb7-b9f0-4ddad5002996.jpg" /> in the classical SEIR model.</p><p>Finally, when comparing the classical models with the extended NRD model, it can be useful to notice that the</p><p>latter generates the delay SEIR model with two constant delays. In fact, by taking the time derivative of Eqs.5a5d and considering<img src="7-8301637\163ecf6a-4817-4a7d-8dc0-b1b42cf03ec5.jpg" />, one can write:</p><disp-formula id="scirp.21997-formula138996"><label>, (13a)</label><graphic position="anchor" xlink:href="7-8301637\a65a268e-614a-4d50-a4f3-7907189899a9.jpg"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.21997-formula138997"><label>, (13b)</label><graphic position="anchor" xlink:href="7-8301637\044f3802-24ac-4f8a-9ac0-2b989dd3e8c8.jpg"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.21997-formula138998"><label>, (13c)</label><graphic position="anchor" xlink:href="7-8301637\1aa91d0f-c9d2-480a-9ce9-faa5461c8f45.jpg"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.21997-formula138999"><label>. (13d)</label><graphic position="anchor" xlink:href="7-8301637\520c871c-bc77-45f9-98e7-87125f1ec65f.jpg"  xlink:type="simple"/></disp-formula></sec><sec id="s4"><title>4. APPROXIMATE EXPRESSION FOR THE SOLUTION</title><p>By considering the numerical solutions, shown in figures 3(a), (b), to Eq.10 for<img src="7-8301637\14c3d8c8-35dc-4491-8f8d-a8e36b832919.jpg" />, we may consider the following approximate expression for the <img src="7-8301637\2b32e9e1-670c-4c4d-b81b-03dd3e56f323.jpg" /> curves</p><disp-formula id="scirp.21997-formula139000"><label>. (14)</label><graphic position="anchor" xlink:href="7-8301637\0bf69ada-c759-4bce-88af-3beda1664a2a.jpg"  xlink:type="simple"/></disp-formula><p>where the quantities A, μ, and σ are parameters to be determined. We therefore turn our attention to the dynamical eq.10, which we may approximately write as follows:</p><disp-formula id="scirp.21997-formula139001"><label>. (15)</label><graphic position="anchor" xlink:href="7-8301637\57ee44bd-b10d-4b04-b1ac-6b0162d3064e.jpg"  xlink:type="simple"/></disp-formula><p>The above ordinary differential equation can be solved by separation of variable for <img src="7-8301637\721b4ac1-ead7-45e0-810f-4253a40625ba.jpg" /> to give:</p><disp-formula id="scirp.21997-formula139002"><label>. (16)</label><graphic position="anchor" xlink:href="7-8301637\23da429b-51e3-40f8-9026-4943c009526a.jpg"  xlink:type="simple"/></disp-formula><p>where <img src="7-8301637\bab10230-b410-4a38-aa2c-6ba5773f02c9.jpg" /> and<img src="7-8301637\1eab2650-3dde-455b-afbd-0333baed67bd.jpg" />. From the above relation, we find:</p><disp-formula id="scirp.21997-formula139003"><label>. (17)</label><graphic position="anchor" xlink:href="7-8301637\6732c19e-f667-49c6-a392-5d79cd21f0af.jpg"  xlink:type="simple"/></disp-formula><p>In this way, Eq.16 can be written as</p><disp-formula id="scirp.21997-formula139004"><label>. (18)</label><graphic position="anchor" xlink:href="7-8301637\33814ecb-1b19-4916-86ec-93269d1a2529.jpg"  xlink:type="simple"/></disp-formula><p>A relation between the three fitting parameters can be obtained by considering the definition of <img src="7-8301637\d707113c-75d1-41cb-8a72-1a009d0d75f8.jpg" /> in Eq.5c, by setting</p><disp-formula id="scirp.21997-formula139005"><label>. (19)</label><graphic position="anchor" xlink:href="7-8301637\cc35d7c8-9c6f-40ec-ad83-d165b94bcd28.jpg"  xlink:type="simple"/></disp-formula><p>The above implicit relation is rather difficult to disentangle analytically to obtain a two-parameter curve for<img src="7-8301637\641f2d14-e65c-4079-bba2-453219ac7ce4.jpg" />. Therefore, it appears more convenient to keep three fitting parameters in the model. In this way, we find approximate solutions by means of a best fit procedure on the numerically obtained curves shown in figures 3(a), (b), using A, μ, and σ as fitting parameters. In order to fix the ideas, let us start by setting <img src="7-8301637\04073ba5-64db-48e2-90a5-1ca51f59e790.jpg" /> and<img src="7-8301637\d7ee4927-ac42-430e-aa19-694f8c9a40be.jpg" />. By taking r = 0.1, we find the following values for the fitting parameters:<img src="7-8301637\80fe0fea-2e75-4cac-b306-bed1aaf8c488.jpg" />, <img src="7-8301637\afa83c58-df6f-4c91-9633-5d2944d810b3.jpg" />,</p><p><img src="7-8301637\5947c33c-f091-4fef-8de2-6dd3e16642ed.jpg" />. Next, by setting r = 0.3, we find:</p><p><img src="7-8301637\19b868c2-1b87-478a-8aff-9a78574d9eb1.jpg" />, <img src="7-8301637\5f40d14e-1795-48c8-9173-8a633d2d2d3a.jpg" />,<img src="7-8301637\85bd960c-edee-41ef-a7a0-ecc75cf46241.jpg" />. The results of numerical integration (dots) along with the approximate solutions (full lines) are shown in <xref ref-type="fig" rid="fig7">Figure 7</xref>(a) for these two cases, namely, r = 0.1 and r = 0.3. The curves corresponding to the approximate solution (full lines) of Eq. 10, along with the numerical integration results (dots), are represented in figure 7(b). From the curves shown in figures 7(a) and (b), we may notice the good agreement of the approximate solution in the asymptotic region. However, as already noticed in the previous section, Eq. 12 gives a satisfactory description of the asymptotic quantity <img src="7-8301637\23e4f04d-5fd4-49fe-98cf-d9368d24fbf8.jpg" /> for which we may write:</p><disp-formula id="scirp.21997-formula139006"><label>. (18)</label><graphic position="anchor" xlink:href="7-8301637\43be9eb6-7c11-48ed-9948-8d319d149793.jpg"  xlink:type="simple"/></disp-formula><p>The above relation gives similar results to figure 2 and 4 with the advantage of providing a very simple expression for the total number of individuals getting ill during an epidemic outbreak.</p></sec><sec id="s5"><title>5. CONCLUSIONS</title><p>The NRD model [<xref ref-type="bibr" rid="scirp.21997-ref7">7</xref>], describing the time evolution of non-lethal infectious diseases in a fixed-size population of N individuals, has been generalized. In the extended version of the NRD model a quiescent time q, in addition to the recovery time τ, is taken as a delay quantity in the dynamics of the infection. The NRD model is recovered from the extended version by setting q to zero.</p><p>The influence of the delay ratio <img src="7-8301637\c6af8185-8b54-4ad6-92b1-0fb2dd5f4460.jpg" /> on the model dynamics is studied. It is seen that the model predicts that a longer incubation period mitigates the effects of an aggressive infective agent (<img src="7-8301637\6c436995-0d5a-4680-9942-eaebb110c428.jpg" />large). Indeed, as it can be argued from the monotonically decreasing behaviour of the fraction <img src="7-8301637\44c9c714-cd90-4eb9-b4a5-ad79f8edc8c5.jpg" /> of people infected during an epidemic outbreak in the <img src="7-8301637\d589eccd-d0b9-4d5b-908a-20010122aee7.jpg" /> vs. r curves obtained for a fixed value of<img src="7-8301637\da405822-e805-4ed0-88c0-fd15ec4c5ed4.jpg" />, the number of total infections decreases as r increases. Furthermore, the critical value <img src="7-8301637\1a28f982-c10b-43a5-8c23-c4a174da497a.jpg" /> of the statistical parameter<img src="7-8301637\958a339e-1440-4159-a42b-55c0f475b5b7.jpg" />, giving the effectiveness of the interaction between susceptible and infectious individuals, is seen to increase for increasing values of r, according to the empirical formula<img src="7-8301637\c8fd7194-fbfc-4634-8201-7768d9c64b1f.jpg" />, where the quantity a is close to unity and may only depend upon the remaining model parameter<img src="7-8301637\2646f2c4-fb30-470e-b8a1-f186eb781211.jpg" />, which represents the number of infectious individuals at time t = 0. From a comparison between the classical SEIR model and the extended NRD model, one can detect a rather evident symmetry of the latter about a vertical axis passing through the peak values of the <img src="7-8301637\5bd3c659-dd64-4913-9d19-ae9de333a4f6.jpg" /> curves. Owing to these rather simple features, an analytic approximation of the solution of the dynamical equation for normalized variable <img src="7-8301637\6b77ebd2-f968-411d-bae7-a8e4ce5a473b.jpg" /> is proposed. The analytic approximation of the solutions to the dynamical equation is shown to be rather accurate in the asymptotic region. Further analytic work is required to investigate the possibility of reducing, in opportune limits, the number of free parameters adopted in deriving the approximated <img src="7-8301637\eee77ddd-0fb8-4da1-b9c4-947de38f5122.jpg" /> curves.</p></sec><sec id="s6"><title>REFERENCES</title></sec></body><back><ref-list><title>References</title><ref id="scirp.21997-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Anderson, R.M. and May, R.M. (1979) Population biology of infectious diseases: Part I. Nature, 280, 361-367.  
doi:10.1038/280361a0</mixed-citation></ref><ref id="scirp.21997-ref2"><label>2</label><mixed-citation publication-type="other" xlink:type="simple">Anderson, R.M. and May, R.M. (1979) Population biology of infectious diseases: Part II. Nature, 280, 455-461.  
doi:10.1038/280361a0</mixed-citation></ref><ref id="scirp.21997-ref3"><label>3</label><mixed-citation publication-type="other" xlink:type="simple">Hyman, J.M., J. Li and Stanley, E.A. (1999) The differential infectivity and staged progression models for the transmission of HIV. Mathematical Bioscience, 155, 77-109. doi:10.1016/S0025-5564(98)10057-3</mixed-citation></ref><ref id="scirp.21997-ref4"><label>4</label><mixed-citation publication-type="other" xlink:type="simple">Li, M.Y., Graef, J.R., Wang, L. and Karsai, J. (1999) Global dynamics of a SEIR model with varying total population size. Mathematical Bioscience, 160, 191-213.  
doi:10.1016/S0025-5564(99)00030-9</mixed-citation></ref><ref id="scirp.21997-ref5"><label>5</label><mixed-citation publication-type="other" xlink:type="simple">Lipshitch, M.M., Cohen, T., Cooper, B., Robins, J.M., Ma, S., James, L., Gopa-lakrishna, G., Chew, S.K., Tan, C.C., Samore, M.H., Fisman, D. and Murray, M. (2003) Transmission dynamics of Severe Acute Respiratory Syndrome. Science, 300, 1966-1970.  
doi:10.1126/science.1086616</mixed-citation></ref><ref id="scirp.21997-ref6"><label>6</label><mixed-citation publication-type="other" xlink:type="simple">Hethcote, M. (2000) The mathematics of infectious diseases. SIAM Review, 42, 599-653.  
doi:10.1137/S0036144500371907</mixed-citation></ref><ref id="scirp.21997-ref7"><label>7</label><mixed-citation publication-type="other" xlink:type="simple">Noviello, A., Romeo, F. and De Luca, R. (2006) Time Evolution of non-lethal infectious diseases: A semi-continuous approach. European Physical Journal B, 50, 505-511. doi:10.1140/epjb/e2006-00163-4</mixed-citation></ref></ref-list></back></article>