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Applied athematics Letters 25 (212) 156 16 Contents lists available at SciVerse ScienceDirect Applied athematics Letters journal homepage: www.elsevier.com/locate/aml Globally stable endemicity for infectious diseases with information-related changes in contact patterns B. Buonomo a, A. d Onofrio b,, D. Lacitignola c a Department of athematics and Applications, University of Naples Federico, via Cintia, -8126 Naples, taly b Department of Experimental Oncology, European nstitute of Oncology, Via Ripamonti 435, -2141 ilano, taly c Department of Health and otory Sciences - Epidemiology Laboratory, University of Cassino, Campus Folcara, -343 Cassino, taly a r t i c l e i n f o a b s t r a c t Article history: Received 1 October 211 Accepted 11 arch 212 Keywords: athematical epidemiology nformation Behavior Global stability SR and SS epidemic models with information related changes in contact patterns are introduced. The global stability analysis of the endemic equilibrium is performed by means of the Li uldowney geometric approach. Biological implications of the stability conditions are given. 212 Elsevier Ltd. All rights reserved. 1. ntroduction Feedbacks and global stability are among the most important features of all mathematical models in biology [1,2]. n athematical Epidemiology, however, the vast majority of efforts have been devoted to the study of global stability. ndeed, determining under which conditions a disease, independently from the initial burden, either remain endemic or get extinct is probably the most important topic. Recently, however, it is increasingly becoming clear that a realistic epidemic model must include the feedback (FB) that the information about an infectious disease has on its spreading [3 7]. For example, a first type of FB is represented by the case of the so-called rational exemption, that is the family s decision to not vaccinate children as a consequence of a pseudo-rational comparison between the risk from infection and the media driven perceived risk from getting damages from the vaccine. This approach has been applied to several epidemic scenarios, see e.g. [8,9,5,1]. A second type of FB, instead, is the one given by the influence of the information on the behavior of healthy subjects. For example, in [4] the authors focus on simple endemic models, by modelling the social contact rate as a decreasing function of the available information on the present and the past disease prevalence. t is shown that social behavior change alone may trigger sustained oscillations. This indicates that human behavior might be a critical explaining factor of oscillations in time-series of endemic diseases. The modelling idea to represent these distinct FBs is that vaccination decisions, for the first type of FB, and behavioral decisions, for the second type, are formed from an information set, summarised by a new state variable mostly based on the publicly available information on both present and also on the recent past spreading of the disease. n this paper we study the global asymptotic stability of the endemic equilibrium for the second case of FB, and for both SR and SS classes of infectious disease models. Corresponding author. Tel.: +39 2 94375114; fax: +39 2 57489922. E-mail addresses: buonomo@unina.it (B. Buonomo), alberto.donofrio@ifom-ieo-campus.it, z2263@ieo.it (A. d Onofrio), d.lacitignola@unicas.it (D. Lacitignola). 893-9659/$ see front matter 212 Elsevier Ltd. All rights reserved. doi:1.116/j.aml.212.3.16

B. Buonomo et al. / Applied athematics Letters 25 (212) 156 16 157 2. The model The mathematical description of the information dependence is given by a quantity,, called the information index, [8,9,4,5,1]. This index is described by the distributed delay = t g(s(τ), (τ))k p a (t τ)dτ. The term K p a is a delaying kernel, which represents the weight given to past prevalence. Generally, K p a is the density function for a gamma distribution: K p (u) = ap u p 1 e au a, u (p 1)! with a >, p = 1, 2,.... n this case the delay is infinite and centered at p/a (see e.g., [11]), which is the average delay. The function g describes the role played by the state variables in the information dynamics. t may be generally assumed g to be continuous and increasing respect to the. No hypotheses on the dependence of g on S are made at this stage (actually g might be independent on S). However we set g(s, ) = for all S. f p = 1, we get K(t) = a e at, that is a exponentially fading memory. n this case we have, Ṁ = ag(s(t), (t)) a. This possibility to transform an infinite dimensional integro-differential systems into a finite dimensional system of ordinary differential equations is called linear chain trick, [11]. n [4] the following model has been introduced Ṡ = µ(1 S) β()s = β()s (µ + ν) (1) Ṁ = ag() a, where the state variables are: Susceptible individuals (S), nfectious individuals () and the information index (). The function β is required to be a positive decreasing function, β () <. The function g is required to be such that g() =, and g () >. We will prove the global stability result of the endemic equilibrium for g satisfying: g () g(). (2) The simplest example is g() = k, where k (, 1). Another example is g() = /(1 + q), where q is a positive constant. The parameters µ, ν, and a, are positive constants. 3. Basic properties n [4] it has been shown that the set Ω = {(S,, ) : S,, S + 1, g(1)} is positively invariant for model (1). oreover the disease free equilibrium E = (1,, ) is on Ω, as well as its stable manifold, which is the set {(S,, ) Ω : = }. As a consequence, the state variables are strongly persistent, i.e. there exists a ϵ > such that if () >, S() >, and () >, then: lim inf t (t) ϵ > ; lim inf t S(t) ϵ > ; lim inf t (t) ϵ >. Furthermore, model (1) admits a unique endemic equilibrium, E = (S,, ) where S = (µ + ν)/β(g( )), = g( ) and is the unique solution of: µ + ν µ (µ + ν) =. β(g()) n [4] the following stability result has also been shown. Theorem 3.1. Let R = β()/(µ+ν). f R 1, then the disease free equilibrium E is globally asymptotically stable. f R > 1, then E is unstable and the endemic equilibrium E is locally asymptotically stable.

158 B. Buonomo et al. / Applied athematics Letters 25 (212) 156 16 4. Global stability of the endemic equilibrium n this section we analyse the global asymptotic stability of E. The following theorem holds, Theorem 4.1. Assume that g satisfies the inequality (2). f R > 1 and ν > 2β(ϵ ), where ϵ is the constant of uniform persistence, then the endemic equilibrium E of system (1) exists and is globally asymptotically stable with respect to solutions of (1) initiating in the interior of Ω. Proof. We first observe that the Jacobian matrix J(S,, ) corresponding to (1) is: J = µ β() β()s β ()S β() β()s (µ + ν) β ()S. ag () a The second additive compound matrix J [2] (S,, ) is: 2µ ν β()( S) β ()S β ()S J [2] = ag () µ a β() β()s. β() β()s µ ν a Now we take the function, P = P(S,, ) = diag t follows that, and, P f P 1 = diag 1,,., Ṁ, Ṁ, 2µ ν β()( S) β ()S β ()S PJ [2] P 1 = ag () µ a β() β()s, β() β()s µ ν a so that B = P f P 1 + PJ [2] P 1 B11 B = 12, B 22 B 21 where B 11 = 2µ ν β()( S), B 12 = [β ()S, β ()S], B 21 = ag (), T and B 22 = Ṁ µ a β() β() β()s Ṁ. + β()s µ ν a Consider now the norm in R 3 as: (u, v, w) = max { u, v + w }, where (u, v, w) denotes the vector in R 3 and denote by L the Lozinskiĭ measure with respect to this norm. t follows, [12]: L(B) sup{g 1, g 2 } sup{l 1 (B 11 ) + B 12, L 1 (B 22 ) + B 21 }, (4) where B 21, B 12 are matrix norms with respect to the L 1 vector norm and L 1 denotes the Lozinskiĭ measure with respect to the L 1 norm 1. L 1 (B 11 ) = 2µ ν β()( S), (3) (5) 1 i.e., for the generic matrix A = (aij ), A = max 1 k n n j=1 a jk and L(A) = max 1 k n (a kk + n j=1(j k) a jk ).

B. Buonomo et al. / Applied athematics Letters 25 (212) 156 16 159 B 12 = β ()S, B 21 = ag (), (6) and L 1 (B 22 ) = Ṁ µ a + max{, 2β()S ν}. (7) Taking into account of (4) (7), the general expressions of g 1 and g 2 for system (1) are thus: g 1 = 2µ ν β()( S) + β ()S, (8) g 2 = Ṁ µ a + ag () + max{, 2β()S ν}. (9) Observe that system (1) provides the following equalities: Ṁ = β()s (µ + ν), Hence, from (8) one gets, = a g() a. g 1 = µ β() + β ()S, and from (9), g 2 = a g() µ + ag () + max{, 2β()S ν}. Taking into account that β() > and β () it follows: g 1 µ. On the other hand, g 2 can be written as g 2 = µ + a [g () g()] + max{, 2β()S ν}. Taking into account that S 1, β is decreasing and that the state variables are strongly persistent, for large t it follows: g 2 µ + a [g () g()] + max{, 2β(ϵ ) ν} where ϵ is the constant of uniform persistence. From (2) and (3) we obtain, for large t: g 2 µ. Hence from (4), Therefore L(B) sup{g 1, g 2 } = µ. 1 t t which implies lim sup t L(B)ds 1 t 1 sup x Γ t t log (t) () µ, L(B(x(s, x )))ds <, so the Bendixson criterion given in [13] is thus verified. # Remark. Note that (3) and R > 1 together imply that 2β(ϵ ) < ν < β().

16 B. Buonomo et al. / Applied athematics Letters 25 (212) 156 16 5. A SS case n this section we briefly analyse the impact of the information-driven behavior of susceptible subjects on the transmission of a SS communicable disease. By including the variable contact rate β() in the classical SS model we obtain the following system: Ṡ = µ(1 S) β()s + γ = β()s (µ + γ ) (1) Ṁ = ag() a. We can study the model on the plane (limit set) S + = 1. odel (1) reduces to: = β()(1 ) (µ + γ ) = F(, ) Ṁ = ak a = G(, ). System (11) has two equilibrium points: a disease-free one, E = (, ), and an endemic equilibrium E = ( e, k e ), where e is the solution of the following equation β(k) = µ + γ 1, which exists only if β() > µ + γ. As far as the behaviour of the solutions of system (11), the following proposition holds. Theorem 5.1. Let R = β()/(µ+ν). f R 1, then the disease free equilibrium E is globally asymptotically stable. f R > 1, then E is unstable and the endemic equilibrium E is globally asymptotically stable. Proof. From the following differential inequality [β()(1 ) (µ + γ )], it follows that R 1 implies the global stability of E. On the contrary, simple linearization shows that E is unstable for R > 1. The global stability of E may be proven by applying the Bendixson Dulac criterion. ndeed, by taking the Dulac function D = 1/, it follows that: Ṡ div, = β() a <, so the locally stable equilibrium E is globally stable. # 6. Conclusions Our results on the global stability of the endemic equilibrium might have implications of some interest in public health. ndeed, for diseases where R > 1, the health authorities can recommend mass vaccination or make it mandatory if the disease is severe or causes economic damage. However, anti-vaccination lobbies could claim that modifying the behavior in the case of an epidemic might be sufficient to eradicate the disease. On the contrary, our results analytically show that this claim is not true for an SS transmission mechanism, since independently on the initial state the infection will remain endemic in the target population. n the SR case, we provide the sufficient condition (3), which guarantees the global stability of the endemic state. References [1] V. Capasso, athematical Structures of Epidemic Systems, in: Lecture Notes in Biomathematics, Springer-Verlag, Berlin, 28. [2] J.D. urray, athematical Biology, third ed., in: nterdisciplinary Applied athematics, vol. 17, Springer-Verlag, New York, 22. [3] C. Bauch, D. Earn, Vaccination and the theory of games, PNAS 11 (24) 13391 13394. [4] A. d Onofrio, P. anfredi, nformation-related changes in contact patterns may trigger oscillations in the endemic prevalence of infectious disease, J. Thor. Biol. 256 (29) 473 478. [5] A. d Onofrio, P. anfredi, E. Salinelli, Vaccinating behaviour, information, and the dynamics of SR vaccine preventable diseases, Theor. Popul. Biol. 71 (27) 31 317. [6] T. Reluga, C. Bauch, A. Galvani, Evolving public perceptions and stability in vaccine uptake, ath. Biosci. 24 (26) 185 198. [7] R. Vardavas, R. Breban, S. Blower, Can influenza epidemics be prevented by voluntary vaccination? PLoS Comp. Biol. 3 (27) e85. [8] B. Buonomo, A. d Onofrio, D. Lacitignola, Global stability of an SR epidemic model with information dependent vaccination, ath. Biosci. 216 (28) 9 16. [9] B. Buonomo, A. d Onofrio, D. Lacitignola, Rational exemption to vaccination for non-fatal SS diseases: globally stable and oscillatory endemicity, ath. Biosci. Engin. 7 (21) 561 578. [1] A. d Onofrio, P. anfredi, E. Salinelli, Fatal SR diseases and rational exemption to vaccination, ath. ed. Biol. 25 (28) 337 357. [11] H. Smith, An ntroduction to Delay Differential Equations with Applications to the Life Sciences, in: Text in Applied athematics, vol. 57, Springer- Verlag, New York, 211. [12] R.H. artin Jr., Logarithmic norms and projections applied to linear differential systems, J. ath. Anal. Appl. 45 (1974) 432 454. [13].Y. Li, J.S. uldowney, A geometric approach to global-stability problems, SA J. ath. Anal. 27 (1996) 17 183. (11)