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Scientific Reports logoLink to Scientific Reports
. 2023 Aug 20;13:13550. doi: 10.1038/s41598-023-40745-x

Mathematical assessment of monkeypox disease with the impact of vaccination using a fractional epidemiological modeling approach

Botao Liu 1, Samreen Farid 2, Saif Ullah 3, Mohamed Altanji 4, Rashid Nawaz 2, Shewafera Wondimagegnhu Teklu 5,
PMCID: PMC10440346  PMID: 37599330

Abstract

This present paper aims to examine various epidemiological aspects of the monkeypox viral infection using a fractional-order mathematical model. Initially, the model is formulated using integer-order nonlinear differential equations. The imperfect vaccination is considered for human population in the model formulation. The proposed model is then reformulated using a fractional order derivative with power law to gain a deeper understanding of disease dynamics. The values of the model parameters are determined from the cumulative reported monkeypox cases in the United States during the period from May 10th to October 10th, 2022. Besides this, some of the demographic parameters are evaluated from the population of the literature. We establish sufficient conditions to ensure the existence and uniqueness of the model’s solution in the fractional case. Furthermore, the stability of the endemic equilibrium of the fractional monkeypox model is presented. The Lyapunov function approach is used to demonstrate the global stability of the model equilibria. Moreover, the fractional order model is numerically solved using an efficient numerical technique known as the fractional Adams-Bashforth-Moulton method. The numerical simulations are conducted using estimated parameters, considering various values of the fractional order of the Caputo derivative. The finding of this study reveals the impact of various model parameters and fractional order values on the dynamics and control of monkeypox.

Subject terms: Computational biology and bioinformatics, Mathematics and computing

Introduction

Monkeypox is a viral disease caused by the monkeypox virus (MPXV), which belongs to the Orthopoxvirus genus. It primarily affects animals, particularly monkeys, squirrels, and rodents. It is a zoonotic disease that can be transmitted to humans through animals. Human-to-human transmission can also occur via close contact with infected individuals, particularly through respiratory droplets or contact with skin lesions or other body fluids. Besides these, other possible modes of transmission include contact with contaminated objects or surfaces known as environmental transmission. Although, infected cases are found in numerous countries in the world, but Africa is the main place where it is most commonly found. The first monkeypox case was identified in 1958 following the occurrence of outbreaks in a group of monkeys that were being studied. Globally, there have been a total of 88,122 reported cases of infection, with 30,555 of these cases occurring in the United States1. The symptoms of monkeypox virus infection in humans are comparable to smallpox signs but less severe2,3. Typically, the infection begins with a fever, headache, muscle pain, and tiredness3. The primary distinction between the symptoms of monkeypox and smallpox is that the monkeypox infection results in lymphadenopathy, characterized by the swelling of lymph nodes3. The incubation period for this infection usually ranges from 7 to 14 days, although it can vary between 5 and 21 days1,3. Symptoms of monkeypox are usually mild, and the majority of patients naturally recover within a few weeks. Those with weakened immune systems may exhibit severe symptoms1,2,4,5. Smallpox and human monkeypox are clinically related due to their difficult-to-distinguish characteristics2. Typically, monkeypox is spread to humans through contact with animal blood or bites from rodents, pets, and primates2,3. Gambian pouched rats (Cricetomys Gambians), dormice (Graphiurus sp.), and African squirrels (Heliosciurus and Funisciurus) have also been found to be infected4. Currently, no approved and safe treatment mechanism specifically for monkeypox virus infection. Nevertheless, some particular controlling measures can be used to mitigate the spread of monkeypox. Vaccines, immune globulin, and antiviral medications introduced for smallpox control can be employed to control the transmission. However, that the smallpox vaccine is currently unavailable as smallpox has been eradicated worldwide6,7.

Monkeypox has received little attention in the past, making it difficult to understand its epidemiology. Despite this, numerous mathematical models have been recently developed to analyze the dynamics of the monkeypox. A novel mathematical model based on deterministic approach for the monkeypox outbreak was developed and examined in8. Their findings revealed that isolating infected people from other populations reduces disease incidence. In9 the authors developed a system of nonlinear differential equations to analyze different modes of monkeypox transmission. The numerical simulation indicates that the immunological status of an individual affects how well they recover from an orthopoxvirus infection. To learn more about the mechanisms of transmission and various controlling methods, many epidemic models on infectious disease have been investigated8,1013. In14 authors developed a mathematical model to better comprehend the dynamics of the monkeypox. Their results suggest the monkeypox outbreak can be eradicated through the proper implementation of non-pharmaceutical interventions. Additionally, in the study of15, the numerical simulation of the model demonstrated that the treatment will result in the elimination of infected individuals from human and non-human primate populations throughout the course of the investigation. Recently, in16,17 the authors introduce a mathematical model with environmental transmission to study the dynamics and some controlling measures of the monkeypox 2022 outbreak.

Mathematical modeling with fractional differential equations has recently attracted the attention of researchers in a wide range of scientific and professional domains, particularly in epidemiology1820. The memory effect is one of the remarkable characteristics of fractional-order models that cannot be developed in classical models because of the numerous properties of fractional operators21,22. Many researchers have recently employed fractional differential equations to represent a variety of infectious and non-infectious diseases. One of these study subjects that has received great attention and produced insightful results is the COVID-19 infection. Mathematical models for COVID-19 based on the fractional derivatives are taken into account in2327. The dynamics of monkeypox with cross-infection via a novel stochastic model was studied in28. A novel modeling approach based on fractal-fractional operators demonstrating monkeying dynamics with animal-to-human transmission was proposed in29.

This study analyzes the dynamics of monkeypox under some controlling measures using fractional-order calculus. We present a comprehensive theoretical and numerical analysis of the fractional order epidemic model. Most of the model parameters are estimated from the actual data set of the monkeypox 2022 outbreak. The description of the manuscript’s main sections is as follows: The section titled “Basic definitions” introduces some fundamental concepts of fractional derivatives. The proposed monkeypox model and parameter estimation are described in section “Formulation of the integer order monkeypox model”. The model’s qualitative analysis is presented in section “Basic analysis of the fractional monkeypox model”. A graphical interpretation of the basic reproduction number versus model parameters is presented in section “Interpretations of R0 versus model parameters”. Detailed numerical treatment for the fractional model is accomplished in section “Numerical results of the fractional model”. Finally, in the last section titled “Conclusion,” we summarized with a conclusion.

Basic definitions

Fractional differential operators in mathematical modeling are well-known and it has been successful in the fields like science, engineering, and epidemiology. We give a few fundamental definitions along with some proprieties that be will used in the rest of the study30,31.

Definition 1

The left and right Caputo fractional derivative operator of the function fL(R)C(R) is defined as follows

t0cDtϑft=t0Dt-m-ϑddtmft=1Γm-ϑt0tt-lm-ϑ-1fmldl,andtcDTϑft=tDT-m-ϑ-ddtmft=-1mΓm-ϑtTl-tm-ϑ-1fmldl. 1

Definition 2

For xR, the generalized Mittag-Leffler function Eα,β(x) is defined by

Eα,βx=m=0xmΓαm+β,α,β>0, 2

and satisfies the following property given in

Eα,βx=xEα,α+βx+1Γβ. 3

The Laplace transform of the function tβ-1Eα,β±λtα is defined as follows

Ltβ-1Eα,β±λtα=sα-βsαλ. 4

Proposition 2.1

Let, fL(R)C(R) and αR, m-1<α<m then the following condition hold

1.t0cDtϑIϑft=ft.2.Iϑt0cDtϑft=ft-k=0m-1tkk!fkt0.

Formulation of the integer order monkeypox model

The total human population Nh is divided into six different compartments i.e Sh susceptible humans, Eh exposed humans, Ih infected humans, Ch clinically ill humans, Vh vaccinated humans and Rh recovered individuals. Similarly, Nr represents the overall non-human population which is further divided into four different subgroups i.e. Sr susceptible, Er exposed, Ir infected and Rr recovered animals respectively.

The susceptible human class is initiated through recruited rate ϕh. This population is declined by the natural mortality rate μh and by the population gaining infection after interacting with infected humans (or animals) at the contact rate β1 or β2 respectively. The susceptible human group is also decreased by vaccinating at the rate αh. This class is further increased by the vaccinated population after waning the induced immunity at the rate η. Thus, the dynamics of the susceptible human class are modeled via the following equation

dShdt=ϕh-β1Ih+β2IrNhSh-μh+αhSh+ηVh.

The class of exposed individuals is increased by joining the newly infected individuals with the force of infection λh=β1Ih+β2IrNh. Moreover, this population class is declined by the transmission rate β and the mortality rate μh. Thus, we obtained the following differential equation describing the dynamics of exposed human class

dEhdt=β1Ih+β2IrNhSh-μh+βEh.

The number of infected people rises at a rate of β after the transition from being exposed class. This class is decreased by the natural death rate μh, the disease-induced death rate δ1, the recovered population at the ω1 and by the people who became clinically ill and join next class at the rate γ. Thus, the resulting dynamics can be modeled via the following equation

dIhdt=βEh-ω1+γ+μh+δ1Ih.

The people in Ih class become clinically (or critically) ill at the rate γ and join Ch class. These individuals are reduced by natural mortality rate μh and disease-induced death rate δ2. Further, it is decreased by joining the recovered class at the rate ρ. Hence, we obtained the following equation describing the dynamics of Ch population

dChdt=γIh-ρ+μh+δ2Ch.

The susceptible individuals are vaccinated at the rate αh. The vaccinated individuals are decreased due to natural mortality rate μh and due to the waning of induced immunity at a rate η. Thus, we have

dVhdt=αhSh-(μh+η)Vh.

Finally, the class of recovered humans is formed due to the transition of individuals from Ih and Ch at the recovery rates ρ and ω1 respectively. Further, it is decreased due to the natural death rate μh. Thus, we obtain

dRhdt=ρCh+ω1Ih-μhRh.

The recruitment rate of susceptible animals is ϕr and the natural death rate in all animal populations is denoted by μr. The force of infection in this case is given by

λr=β3IrNr,

where β3 is the effective contact rate causing the disease transmission rate among animals. The flow from exposed to the infected animal compartment is denoted by ε. The death rate induced due to infection in infected animals is δ3. The parameter ω2 shows the recovery rate of infected animals. Thus, the dynamics of monkeypox in animals are given by the following system

dSrdt=ϕr-β3IrNrSr-μrSr,dErdt=β3IrNrSr-ε+μrEr,dIrdt=εEr-ω2+μh+δ3Ir,dRrdt=ω2Ir-μrRr. 5

Fractional monkeypox model in the Caputo sense

This section presents the extension of the integer order monkeypox model to the fractional case. The well-known Caputo derivative having order 0<ϑ1 is utilized to formulate the generalized fractional epidemic model. Fractional epidemic models used fractional derivatives to capture more complex and non-local effects in the disease transmission dynamics. Such epidemic models have a greater degree of freedom and offer insights into the behavior and control of infectious diseases for a particular set of data22. The proposed model for transmission of monkeypox model is described by the following system

cDtϑSh=ϕh-λhSh-k1Sh+ηVh,cDtϑEh=λhSh-k2Eh,cDtϑIh=βEh-k3Ih,cDtϑCh=γIh-k4Ch,cDtϑVh=αhSh-k5Vh,cDtϑRh=ρCh+ω1Ih-μhRh,cDtϑSr=ϕr-λr+μrSr,cDtϑEr=λrSr-k6Er,cDtϑIr=εEr-k7Ir,cDtϑRr=ω2Ir-μrRr, 6

where,

k1=μh+αh,k2=μh+β,k3=ω1+γ+μh+δ1,k4=δ+μh+δ2,k5=μh+η,k6=ε+μrk7=ω2+μh+δ3.

Subject to non-negative initial conditions

Sh0=Sh0,Eh0=Eh0,Ih0=Ih0,Ch0=Ch0,Vh0=Vh0,Rh0=Rh0,Sr0=Sr0,Er0=Er0,Ir0=Ir0andRr0=Rr0. 7

Parameter estimation and data fitting

The objective of the present section is to accomplish the parameter estimation of the model. The estimation procedure is performed in two ways. Most of the model parameters are estimated from the real statistics of infected cases reported from 10 May to the end of October 2022 in the recent outbreak in the USA1,3. While some of the demographic parameters (the natural death and birth rate) are estimated from the USA population32. The estimation of parameters from the real disease data is significant for carrying out the numerical simulations more realistically. The estimation process of the proposed model (6) is conducted using the well-known nonlinear least square technique.

This procedure involves the following main steps:

  1. Define an objective function for quantifying the difference between the predicted and the actual data. This function is mathematically expressed as the sum of squared residuals (SSR) between the model predictions and the corresponding actual data points.

  2. Define or set the model parameters’ initial values that need to be estimated. These values can be based on prior knowledge or initial guesses.

  3. Utilizing the initial parameter values set in step 2, the epidemic model is simulated in order to generate model predictions.

  4. Using a ’lsqcurvefit’ optimization technique, for the minimization of objective function.

  5. Set a convergence criterion to stop the iterative estimation scheme. This criterion is based on a maximum number of iterations, a minimal change in parameter estimates, or attaining a predefined threshold for the corresponding objective function.

  6. If the estimated parameter values do not adequately fit the real data curve or do not meet the convergence criterion, reset the initial parameter estimates and re-execute steps 3–5 until a reasonable agreement between the model simulation and the actual data is obtained.

By iteratively minimizing the objective function via a standard nonlinear least squares technique, the parameter estimates are refined, which leads to improved agreement between the model-predicted and observed data. The fitted and estimated values of the monkeypox epidemic model’s parameters are listed in Table 1, while Fig. 1 illustrates the model’s good fit to the observed data.

Table 1.

Fitted and estimated values of the model parameters.

Parameter Description Value in days References
ϕh Birth rate of humans 11731.91 32
ϕr Birth rate of animals or rodents 0.016 8
η Waning induced immunity 0.2010 Fitted
ρ Recovery rate of Ch 0.0843 Fitted
β Transition rate of Eh to Ih 0.0486 Fitted
γ Moving of Ih to Ch 0.1119 Fitted
β3 Contact rate of Sr and Ir 0.2461 Fitted
β1 Contact rate of Sh and Ih 0.5701 Fitted
β2 Contact rate between Ir and Sh 0.2508 Fitted
αh Vaccinated against monkeypox 0.2393 Fitted
μh Natural death rate of humans 1/(79*365) 32
δ1 Disease induced mortality rate of infectious human 0.0011 Fitted
δ2 Disease-induced rate of Ch 1.0091e−04 Fitted
δ3 Disease induced death rate of infected animals 1.5303e−05 Fitted
ω1 Permanent immunity due to treatment 0.4670 Fitted
μr Natural death rate of animals 0.000016 8
ω2 Recovery rate due to immunity 0–1 Assumed
ϵ Progression from being Er to Ir 0.1053 Fitted

Figure 1.

Figure 1

Model predicted curve (solid line) to the observed data for the case when ϑ=1.

Basic analysis of the fractional monkeypox model

In this section, we address some of the basic and necessary mathematical analysis of the fractional monkeypox epidemic model (6). We proceed as follows

Positivity and boundedness

For the positive initial values limtsupNhtϕhμhandlimtsupNrtϕrμr. Also, if Nh0tϕhμhandNr0tϕrμr then the feasible domain for the given system is given by

Ωh=Sh,Eh,Ih,Ch,Vh,RhR+6:Sh+Eh+Ih+Ch+Vh+Rhϕhμh,Ωr=Sr,Er,Ir,RrR+4:Sr+Er+Ir+Rrϕrμr,

such that Ω=Ωh×ΩrR+6×R+4 and we have Ω is positively invariant.

Let Sh0Eh0,Ih0,Ch0,Vh0,Rh0, Sr0,Er0,Ir0 and Rr0 be positive, then all solution are will be positive for t>0. Considering the first equation in (6) we have

cDtϑSh=ϕh-λh+k1Sh+ηVh,

then

cDtϑSh+λh+k1Sh=ϕh+ηVh.

Since ϕh+ηVh0 therefore, it implies

cDtϑSh+λh+k1Sh0.

By using the Laplace transform we have

LcDtϑSh+Lλh+k1Sh0,sϑShs-sϑ-1Sh0+λh+k1Shs0,Shssϑ-1sϑ+λh+k1Sh0.

Applying inverse Laplace transform we have

ShtEϑ,1-λh+k1tϑSh0.

Since, quantities on right hand side are positive so we have Sh0 for t0. In similar approach, we have Eh,Ih,Ch,Vh,Rh,Sr,Er,IrandRr0t>0 corresponding to any non-negative initial values. Thus, the solution remain in R+6×R+4 for all t>0 with non-negative initial values.

Next to we prove the boundedness of the fractional model solution. The total human individuals is given by

Nht=Sht+Eht+Iht+Cht+Vht+Rht,

such that

cDtϑNht=cDtϑSht+cDtϑEht+cDtϑIht+cDtϑCht+cDtϑVht+cDtϑRht,cDtϑNht=ϕh-δ1Ih+δ2Ch-μhNhtϕh-μhNt,cDtϑNhtϕh-μhNht.

Taking Laplace transform on both sides we have

LcDtϑNhtLϕh-μhNht,sϑNhs-sϑ-1Nh0+μhNhsϕhs,Nhssϑ-1sϑ+μhNh0+ϕhssϑ+μh.

By applying inverse Laplace transform we have

NhtEϑ,1-μhtϑNh0+ϕhEϑ,ϑ+1-μhtϑ. 8

By taking limit t we have Nh(t)ϕhμh implies that limtsupNht=ϕhμh. If Nh0ϕhμh then Nhtϕhμh which implies Nh(t) is bounded. In similar way, we can prove that Nr(t) is bounded. Therefore, this established the notion of the set Ω as required. So, we conclude that the region is epidemiological feasible and well posed in Ω.

Existence and uniqueness

Let T be a positive real number and consider J=[0,T]. We denote the set of all continuous function defined on J by Ce0(J) with norm as X=supXt,tJ. Consider the system (6), (7) as following initial value problem (I.V.P.)

cDtϑXt=Ft,Xt,0<t<T<,X0=X0, 9

where X(t)=(Sh(t),Eh(t),Ih(t),Ch(t),Vh(t),Rh(t),Sr(t),Er(t),Ir(t),Rr(t)) represents the compartments and F is continuous function defined as follows

Ft,Xt=F1t,ShtF2t,EhtF3t,IhtF4t,ChtF5t,VhtF6t,RhtF7t,SrtF8t,ErtF9t,IrtF10t,Rrt=ϕh-β1Ih+β2IrNh+μhSh-αhSh+ηVhβ1Ih+β2IrNhSh-μh+βEhβEh-ω1+γ+μh+δ1IhγIh-ρ+μh+δ2ChαhSh-μhVh-ηVhρCh+ω1Ih-μhRhϕr-β3IrNr+μrSrβ3IrNrSr-ε+μrErεEr-μr+δ3+ω2Irω2Ir-μrRr. 10

Using property (2.1) in proposition we have

Sht=Sh0+Itϑϕh-β1Ih+β2IrNh+μhSh-αhSh+ηVh,Eht=Eh0+Itϑβ1Ih+β2IrNhSh-μh+βEh,Iht=Ih0+ItϑβEh-ω1+γ+μh+δ1Ih,Cht=Ch0+ItϑγIh-ρ+μh+δ2Ch,Vht=Vh0+ItϑαhSh-μhVh-ηVh,Rht=Rh0+ItϑρCh+ω1Ih-μhRh,Srt=Sr0+Itϑϕr-β3IrNr+μrSr,Ert=Er0+Itϑβ3IrNrSr-ε+μrEr,Irt=Ir0+ItϑεEr-μr+δ3+ω2Ir,Rrt=Rr0+Itϑω2Ir-μrRr.

The Picard iterations lead as follows

Shnt=Sh0+1Γϑ0tt-lϑ-1F1l,Shn-1ldl,Ehnt=Eh0+1Γϑ0tt-lϑ-1F2l,Ehn-1ldl,Ihnt=Ih0+1Γϑ0tt-lϑ-1F3l,Ihn-1ldl,Chnt=Ch0+1Γϑ0tt-lϑ-1F4l,Chn-1ldl,Vhnt=Vh0+1Γϑ0tt-lϑ-1F5l,Vhn-1ldl,Rhnt=Rh0+1Γϑ0tt-lϑ-1F6l,Rhn-1ldl,Srnt=Sr0+1Γϑ0tt-lϑ-1F7l,Srn-1ldl,Ernt=Er0+1Γϑ0tt-lϑ-1F8l,Ern-1ldl,Irnt=Ir0+1Γϑ0tt-lϑ-1F9l,Irn-1ldl,Rrnt=Rr0+1Γϑ0tt-lϑ-1F10l,Rrn-1ldl.

Final transformation of the I.V.P. (9) can be written as follows

Xt=X0+1Γϑ0tt-lϑ-1Fl,Xldl. 11

Lemma 1

The vector F(tX(t)) described in (10) fulfills the well-known Lipschitz condition in the variable X on a set [0,T]×R+10 with Lipschitz constant

ψ=maxβ1+β2+μh,μh+β,μh+δ1+γ+ω1,μh+ρ+δ2,μh+η,μh,μr+β3,μr+ε,μr+ω2+δ3,μr.

Proof

F1t,Sh-F1t,Sh1=ϕh-β1Ih+β2IrNh+μhSh-αhSh+ηVh-ϕh-β1Ih+β2IrNh+μhSh1-αhSh1+ηVh=-β1Ih+β2IrNhSh-Sh1+μhSh-Sh1β1+β2Sh-Sh1+μhSh-Sh1β1+β2+μhSh-Sh1.

Similarly,

F2t,Eh-F2t,Eh1μh+βEh-Eh1,F3t,Ih-F3t,Ih1μh+δ1+γ+ω1Ih-Ih1,F4t,Ch-F4t,Ch1μh+ρ+δ2Ch-Ch1,F5t,Vh-F5t,Vh1μh+ηVh-Vh1,F6t,Rh-F6t,Rh1μhRh-Rh1,F7t,Sr-F7t,Sr1μr+β3Sr-Sr1,F8t,Er-F8t,Er1μr+εEr-Er1,F9t,Ir-F9t,Ir1μr+ω2+δ3Ir-Ir1,F10t,Rr-F10t,Rr1μrRr-Rr1.

Combining all these we have

Ft,X1t-Ft,X2tψX1-X2,ψ=maxβ1+β2+μh,μh+β,μh+δ1+γ+ω1,μh+ρ+δ2,μh+η,μh,μr+β3,μr+ε,μr+ω2+δ3,μr. 12

Lemma 2

Suppose we have (12) then the I.V.P. (6), (7) have unique solution XtCe0J.

Proof

For the required result, the fixed point theory and Picard-Lindelöf is used. Solution of the (6), (7) is considered as X(t)=W(X(t)), where W is the Picard operator defined as W:Ce0J,R+10Ce0J,R+10

WXt=X0+1Γϑ0tt-lϑ-1Fl,Xldl.

Further, it leads to

WX1t-WX2t=1Γϑ0tt-lϑ-1Fl,X1l-Fl,X2ldl1Γϑ0tt-lϑ-1Fl,X1l-Fl,X2ldlψΓϑ0tt-lϑ-1X1-X2dlψΓϑ+1W.

If ψΓϑ+1W<1, then W gives a contraction and therefore, the problem (6), (7) has a unique solution.

Model equilibria and the basic reproduction number R0

The model disease free equilibrium (DFE) is given by

D0=Sh0,Eh0,Ih0,Ch0,Vh0,Rh0,Sr0,Er0,Ir0,Rr0=k5ϕhk1k5-ηαh,0,0,0,αhϕhk1k5-ηαh,0,ϕrμr,0,0,0. 13

Using the next generation method33 we compute the basic reproduction number R0. Let x=Eh,Ih,Ch,Vh,Er,Ir then we have

dxdt=F-V,

where

F=β1Ih+β2IrShNh000β3SrIrNr0,V=k2Ehk3Ih-βEhk4Ch-γIhk5Vh-αhShk6Erk7Ir-εEr.

Then we considered the Jacobian of the Linearized system at disease free state which is given by

F=0β1Sh0Nh0000β2Sh0Nh000000000000000000000000β3Sr0Nr0000000,V=k200000-βk300000-γk4000000k5000000k600000-εk7.

Where, F and V are 6×6 matrices calculated as F=FixjD0 and V=VixjD0. Also, F and V contains the linear and non-linear terms of infected compartments. So, the reproduction number is calculated as

R0=ρFV-1=maxRr0,Rh0=maxεβ3k6k7,ββ1Sh0k2k3Nh0. 14

Existence of endemic equilibrium point

The endemic equilibrium (EE) of the fractional monkeypox model is given by

ζ=Sh,Eh,Ih,Ch,Vh,Sr,Er,Ir,Rr,

and is defined as follows

Sh=k5ϕhk1+λhk5-ηαh,Eh=λhk5ϕhk2k1+λhk5-ηαh=λhk2Sh,Ih=βλhk5ϕhk2k3k1+λhk5-ηαh=βλhk2k3Sh=d1λhSh,Ch=βγλhk5ϕhk2k3k4k1+λhk5-ηαh=βγλhk2k3k4Sh=d2λhSh,Vh=αhϕhk1+λhk5-ηαh=αhShk5=d3λhSh,Rh=--βγρλhk5ϕh-βk4k5λhϕhω1k2k3k4k1+λhk5-ηαhμh=d4λhSh+d5λhSh,Sr=ϕrλr+μr,Er=λrϕrk6μr+λr=λrk6Sr=d6λrSr,Ir=ελrϕrk6k7λr+μr=λrεk6k7Sr=d7λrSr,Rr=ελrϕrω2k6k7μrλr+μr=λrεω2k6k7μrSr=d8λrSr, 15

where, d1=ζk3,d2=γd1k4,d3=αhk5,d4=ρd2μh,d5=ζω1k2k3μh,d6=1k6,d7=εd6k7,d8=d6+d7andd9=β2β3d8.

Moreover,

λr=β3IrNr=Rr0-1d6+d7+d8=Rr0-1d9, 16
λh=β1Ih+β2β3Rr0-1d9NrNh, 17

by using (16) in (17) we have

λh=β1IhNh+Rr0-1Nrd9Nh, 18

Global stability at EE

In the system (6) λh=β1IhNh+β2IrNh and λr=β3IrNr. Also Nhϕhμh,Nrϕrμrast, therefore, we have λh1=α3Ih+α4Irand λr1=α5Ir. Therefore, the system (6) becomes

cDtϑSh=ϕh-λh1Sh-k1Sh+ηVh,cDtϑEh=λh1Sh-k2Eh,cDtϑIh=βEh-k3Ih,cDtϑCh=γIh-k4Ch,cDtϑVh=αhSh-k5Vh,cDtϑRh=ρCh+ω1Ih-μhRh,cDtϑSr=ϕr-λr1+μrSr,cDtϑEr=λr1Sr-k6Er,cDtϑIr=εEr-k7Ir,cDtϑRr=ω2Ir-μrRr. 19

Results for system (19) at steady states are calculated as follows

ϕh=λh1Sh+k1Sh-ηVh,k2Eh=λh1Sh,k3Ih=βEh,k4Ch=γIh,k5Vh=αhSh,ϕr=λr1+μrSr,k6Er=λr1Sr,k7Ir=εEr.

Theorem 4.1

If R0>1, then (19) at EE ζ is global asymptotic stability (GAS) if 6-ShSh+λh1λh11-ShEhShEh-IhEhIhEh-ChCh-ChIhChIh-SrSr+λr1λr11-SrErSrEr-IrIr-IrErIrEr0.

Proof

Consider the following nonlinear Lyapunov function given by (20)

Mt=Mht+Mrt,=M1Sh-Sh-ShlnShSh+M2Eh-Eh-EhlnEhEh+M3Ih-Ih-IhlnIhIh+M4Ch-Ch-ChlnChCh+M5Vh-Vh-VhlnVhVh+M6Sr-Sr-SrlnSrSr+M7Er-Er-ErlnEhEr+M8Ir-Ir-IrlnIrIr. 20

The Caputo fractional derivative of (20) implies

cDtϑMt=cDtϑMht+cDtϑMrt,M11-ShShcDtϑSht+M21-EhEhcDtϑEht+M31-IhIhcDtϑIht+M41-ChChcDtϑCht+M51-VhVhcDtϑVht+M61-SrSrcDtϑSrt+M71-ErErcDtϑErt+M81-IrIrcDtϑIrt,=λr1Sr(1-ShShcDtϑSht+1-EhEhcDtϑEht+k2β1-IhIhcDtϑIht+k2k3γβ1-ChChcDtϑCht+k1αh1-VhVhcDtϑVht)+λh1Sh(1-SrSrcDtϑSrt+1-ErErcDtϑErt+k6ε1-IrIrcDtϑIrt),1-ShShcDtϑSh=1-ShShλh1Sh+k1Sh-ηVh-λh1Sh-k1Sh+ηVh,=λh1Sh1-Shλh1Shλh1-ShSh+λh1λh1+k1Sh2-ShSh-ShSh-ηVh1-VhVh1-ShSh,1-EhEhcDtϑEh=1-EhEhλh1Sh-λh1ShEhEh,=λh1Sh1-Shλh1Shλh1EhEh-EhEh+Shλh1Shλh1,k2β1-IhIhcDtϑIh=k2β1-IhIhβEh-k3IhIhIh,=λh1Sh1+EhEh-IhIh-EhIhEhIh,k2k3γβ1-ChChcDtϑCh=k2k3γβ1-ChChIhIh-ChCh,=λh1Sh1-ChCh-IhChIhCh+IhIh,k1αh1-VhVhcDtϑVh=1-VhVhαhSh-k5VhVhVh,=k1Sh1+ShSh-VhVh-VhShVhSh,1-SrSrcDtϑSr=1-SrSrλr1Sr+μrSr-λr1Sr-μrSr,=λr1Sr1-SrIrSrIr-SrSr+IrIr+μrSr2-SrSr-SrSr,1-ErErcDtϑEr=1-ErErλr1Sr-λr1SrErEr,=λr1Sr1+SrIrSrIr-ErEr-SrIrErSrIrEr,k6ϵ1-IrIrcDtϑEr=1-IrIrεEr-εErIrIr,=λr1Sr1+ErEr-IrIr-ErIrErIr. 21

After replacement in (21) it implies

cDtϑMtλh1Shλr1Sr6-ShSh+λh1λh11-ShEhShEh-IhEhIhEh-ChCh-ChIhChIh-SrSr+IrIr1-SrErSrEr-IrIr-IrErIrEr-k1Shλr1Sr(ShSh-1-lnShSh+VhVh-1-lnVhVh+ShVhShVh-1-lnShVhShVh)-ηVhλr1Sr1-VhVh1-ShSh-μrλh1ShSr(Sr-Sr2SrSr),cDtϑMtλh1Shα5Rr0-1ϕrβ3c9μrSr6-ShSh+λh1λh11-ShEhShEh-IhEhIhEh-ChCh-ChIhChIh-SrSr+λr1λr11-SrErSrEr-IrIr-IrErIrEr-α5Rr0-1ϕrβ3c9μrSrk1ShShSh-1-lnShSh+VhVh-1-lnVhVh+ShVhShVh-1-lnShVhShVh+ηVh1-VhVh1-ShSh-μrλh1ShSrSr-Sr2SrSr.

Thus, cDtϑMt0 for R0>1. Furthermore, cDtϑMt=0 whenever ζ=Sh,Eh,Ih,Ch,Vh,Rh,Sr,Er,Ir. Thus, by LaSalle’s invariance principle the EE is GAS in Ω whenever, R0>1.

Interpretations of R0 versus model parameters

In this section, we analyze the impact of some model parameters on R0. The basic reproduction number R0 is a key biological parameter that plays an important role in describing the disease dynamics and its possible control. In these graphical results, we consider the disease transmission rates β1, β2, vaccination rate αh, recovery rates ρ, ω1 and vaccine waning rate η. The respective graphical results are shown in Figs. 2a, 3, 4, 5 and 6a, while the corresponding contour plots in each case are shown in Figs. 2b, 3, 4, 5 and 6b. Figure 2 shows the combine impact of β1 and αh on R0. It shows that the R0 decreases with a decrease in transmission coefficient β1 and an increase in vaccination rate αh. Further, impact of β2 along with αh upon R0 is demonstrated in the Fig. 3a with the corresponding counter plot 3b. It can be observed that with the increase in vaccination rate and reduction in contact rate β the basic reproduction reduces to a value less than 1. Similarly, the impact of ρ and β2, ω1 and β2, η and αh are presented in Figs. 4a, 5a, and 6a respectively. We can observe that with the decrease in disease transmission rate β2 and enhancement in vaccination rate αh and recovery rate ω the basic reproduction decreases significantly to a value less than unity.

Figure 2.

Figure 2

The subplot (a) illustrate the impact of β1 (disease transmission coefficient relative to Ih) and αh (vaccination rate ) on R0, where (b) shows the respective contour plot.

Figure 3.

Figure 3

The subplot (a) analyze the impact of β2 (disease transmission coefficient relative to Ir) and αh (vaccination rate ) on R0, where (b) shows the respective contour plot.

Figure 4.

Figure 4

The subplot (a) demonstrate the impact of β2 (disease transmission coefficient relative to Ir) and ρ (recovery rate of Ch) on R0, where (b) shows the respective contour plot.

Figure 5.

Figure 5

The subplot (a) demonstrate the impact of β2 (disease transmission coefficient relative to Ir) and ω1 (recovery rate of Ih) on R0, where (b) shows the respective contour plot.

Figure 6.

Figure 6

The subplot (a) demonstrate the impact of αh (vaccination rate) and η (loss of immunity rate) on R0, where (b) shows the respective contour plot.

Numerical results of the fractional model

In this section, we first investigate the numerical solution of the Caputo fractional monkeypox model. The generalized fractional Adams-Bash forth-Moulton approach34, an effective iterative method is used to solve the model numerically. The simulation for different model parameters and different values of ϑ are carried out using the generated numerical technique and the values for model parameters are listed in Table 1. The subsequent subsection contains the iterative solution.

Numerical technique

A concise numerical method for the approximate solution of the monkeypox transmission model in the Caputo sense is shown in this subsection. For this purpose, the fractional Adams-Bashforth-Moulton is used. The system (6) can be recomposed in the subsequent problem to get the desired scheme:

CDtϑv(t)=M(t,v(t)),0<t<T,v(m)(0)=v0(m),m=0,1,,v,v=[ϑ], 22

where, v=(Sh,Eh,Ih,Ch,Vh,Rh,Sr,Er,Ir,Rr)R+10, and M(t,v(t)) shows a continuous real valued function. Using the concept of integral in Caputo case, the aforementioned Eq. (22) is considered as follows:

v(t)=m=0v-1v0(m)tmm!+1Γ(ϑ)0t(t-x)ϑ-1M(x,v(x))dx. 23

In order to use the procedure in34, a uniform grid on [0,T] with step size h=TN, NN, where tu=uh,u=0,1,N is considered. Thus, the proposed model in (6) can be treated as:

Shu+1(t)=Sh0+hϑΓϑ+2{Φh-α1Ihm+α2IrmShmNhm-k1Shm+ηVhm}+hϑΓ(ϑ+2)k=0ubk,u+1{Φh-α1Ihk+α2IrkShkNhk-k1Shk+ηVhk},Ehu+1(t)=Eh0+hϑΓ(ϑ+2){(α1Ihm+α2Irm)ShmNhm+k2Ehm}+hϑΓ(ϑ+2)j=0ubk,u+1{(α1Ihk+α2Irk)ShkNhk+k2Ehk},Ihu+1(t)=Ih0+hϑΓ(ϑ+2){βEhm-k3Ihm}+hϑΓ(ϑ+2)k=0ubk,u+1{Ehk-k3Ihk},Chu+1(t)=Ch0+hϑΓ(ϑ+2){γIhm-k4Chm}+hϑΓ(ϑ+2)k=0ubk,u+1{γIhk-k4Chk},Vhu+1(t)=Vh0+hϑΓ(ϑ+2){αhShm-k5Vhm}+hϑΓ(ϑ+2)k=0ubk,u+1{αhShk-k5Vhk},Rhk+1(t)=Rh0+hϑΓϑ+2{ρChm+ω1Ihm-μhRhm}+hϑΓ(ϑ+2)k=0ubk,u+1{ρChk+ω1Ihk-μhRhk},textsectionru+1(t)=Sr0+hϑΓ(ϑ+2){ϕr-β3IrmNrmSrm-μrSrm}+hϑΓ(ϑ+2)k=0ubk,u+1{ϕr-β3IrkNrkSrk-μrSrk},Eru+1(t)=Er0+hϑΓ(ϑ+2){β3IrmNrmSrm-k6Erm}+hϑΓ(ϑ+2)k=0ubk,u+1{β3IrkNrkSrk-k6Erk},Iru+1(t)=Ir0+hϑΓ(ϑ+2){ϵErm-k7Irm}+hϑΓ(ϑ+2)k=0ubk,u+1{ϵErj-k7Irj},Rrk+1(t)=Rr0+hϑΓ(ϑ+2){ω2Irm-μrRrm}+hϑΓ(ϑ+2)k=0ubi,u+1{ω2Irk-μrRrk},

where,

Shu+1m(t)=Sh0+1Γ(ϑ)k=0uθk,u+1{Φh-α1Ihk+α2IrkShkNhk-k1Shk+ηVhk},Ehu+1m(t)=Eh0+1Γ(ϑ)k=0uθk,u+1{α1Ihk+α2IrkShkNhk-k2Ehk},Ihu+1m(t)=Ih0+1Γ(ϑ)k=0uθk,u+1{βEhk-k3Ihk},Chu+1m(t)=Ch0+1Γ(ϑ)k=0uθk,u+1{ρChk+ω1Ihk-μhRhk},Vhu+1m(t)=Vh0+1Γ(ϑ)k=0uθk,u+1{αhShk-k5Vhk},Rhu+1m(t)=Rh0+1Γ(ϑ)k=0uθk,u+1{ρChk+ω1Ihk-μhRhk},textsectionru+1m(t)=Sr0+1Γ(ϑ)k=0uθk,u+1{ϕr-β3IrkNrkSrk-μrSrk},Eru+1m(t)=Er0+1Γ(ϑ)k=0uθk,u+1{β3IrkNrkSrk-k6Erk},Irk+1m(t)=Ir0+1Γ(ϑ)k=0uθk,u+1{ϵErk-k7Irk},Rru+1m(t)=Rr0+1Γ(ϑ)k=0uθk,u+1{ω2Irk-μrRrk},

Further, we have in the above expressions

bk,u+1=uϑ+1-(u-ϑ)(u+1)ϑ,k=0(u-k+2)ϑ+1+(u-k)ϑ+1-2(u-k+1)ϑ+1,1ku,1,k=u+1,

and

θk,u+1=hϑϑ(u-k+1)ϑ+(u-k)ϑ,0ku.

Simulation of the fractional monkeypox model

In this section, we applied the iterative technique developed in the preceding section in order to simulate the monkeypox Caputo epidemic model (6). The simulation results are illustrated by taking the baseline values of estimated parameters listed in Table 1. In the simulation results, we mainly focus on the dynamics of infected human and animal populations. Initially, in the simulation, we analyze the dynamics of model state variables for various values of ϑ(0,1] to study the impact of memory index on disease incidence. Further, the influence of variation in the recovery rate ω1 on the behavior of the infected human population is predicted for many values of fractional order ϑ. Moreover, we considered different scenarios by decreasing the effective contact rates among susceptible humans and infected animals (i.e., β1,β2) and the parameter β3 showing the effective contact rate between susceptible and infected animals. In addition, these simulations are performed for various non-integer values of the parameter ϑ. The detailed discussion of the aforementioned simulation is described in the following subparts.

Impact of memory index (ϑ)

In the first case of simulation, we illustrate the impact of only fractional order ϑ of the Caputo operator on the model dynamics. The graphical results are shown in Figs. 7a–e and 8a–c. The dynamics of only human population classes are shown in Fig. 7 while Fig. 8 illustrates the dynamical aspects of only animal subpopulation. The simulation in both cases is performed for four values of ϑ=1,0.95,0.90,0.85. The time length considered in the simulation is taken to 500 days. It is observed that under the specific conditions, the solution trajectories in both population classes are converged to the steady state for all values of fractional order ϑ.

Figure 7.

Figure 7

Simulations of only human classes in fractional monkeypox epidemic model (6) for various values of fractional order ϑ.

Figure 8.

Figure 8

Simulations of only non-human classes in fractional monkeypox epidemic model (6) for various values of fractional order ϑ.

Impact of recovery rate ω1 and memory index (ϑ)

In this subpart, we analyzed the impact of variation in recovery rate ω1 on the dynamics of cumulative cases of exposed Eh, infected Ih, and clinically infected Ch human under different values of memory index (ϑ). The parameter showing recovery rate is perturbed with different rates (with baseline and with 10%, 30%, and 50% increase) depending on the treatment strength provided to the infected human population. The resulting simulation is accomplished in Figs. 9, 10 and 11 with subplots (a–c) for three values of fractional order ϑ. It is observed that with an increase in parameter ω1, the infected population in all aforementioned classes reduces showing the impact of treatment on the disease incidence. Additionally, it can observed that in the case of smaller values of ϑ, the decline in the infected population is slightly faster.

Figure 9.

Figure 9

Impact of recovery rate ω1 with ϑ=1.

Figure 10.

Figure 10

Impact of recovery rate ω1 with ϑ=0.90.

Figure 11.

Figure 11

Impact of recovery rate ω1 with ϑ=0.80.

Impact of disease transmission rates and memory index (ϑ)

This section describes the influence of the infection transmission rates β1,β2, and β3 on the dynamics of infected human and animal population classes. The graphical results are initially performed for the baseline values of the aforementioned parameters given in Table 1. Subsequently, the parameter values are decreased with 10%, 20%, 40%, and 50% to the estimated values. Furthermore, the simulation results are presented for three values of fractional order ϑ. These resulting simulations for the human population are shown in Figs. 12, 13 and 14 with respective subplots from (a–c) while the dynamics of the infected animal population are demonstrated in Figs. 12, 13 and 14d, e. In all plots, it is evident that the cumulative infected population significantly decreases as the infection transmission rates are reduced. Moreover, it can be seen from Figs. 13 and 14, that fractional values of ϑ provide more insights enhancing our understanding of the disease dynamics. disease dynamics. Consequently, these graphical interpretations suggest that the effective control of the monkeypox disease and the reduction of disease-induced mortality can be achieved by implementing appropriate treatment and disinfection techniques.

Figure 12.

Figure 12

Impact of contact rates β1,β2,β3 with different rated and ϑ=1.

Figure 13.

Figure 13

Impact of contact ratesβ1,β2,β3 with different rated and ϑ=0.90.

Figure 14.

Figure 14

Impact of contact rates β1,β2,β3 with different rated and ϑ=0.80.

Conclusion

In this manuscript, we analyzed the dynamics of a novel monkeypox infection with the case study of the recently reported outbreak. The model is first formulated using an integer-order nonlinear system of ten differential equations. The human population was divided into six distinct subgroups, while the animal population was divided into four classes. To estimate the model parameters, we fit the model to the actual cases of the 2022 monkeypox outbreak in the USA. Moreover, keeping the importance of the fractional modeling approach, the integer case model is extended to fractional order via the well-known Caputo operator. In the initial stage, we presented a comprehensive theoretical analysis of the fractional monkeypox model, including the existence and uniqueness of the solutions. The existence and stability analysis of the model equilibria are provided. Furthermore, the fractional model is solved numerically using the fractional Adams-Bashforth-Moulton approach. The simulation results illustrate the impact of disease incidence graphically, considering both the baseline values of the parameters and different values of the fractional order of the Caputo operator. Moreover, the model is simulated by increasing the parameter ω1 (the recovery rate) and decreasing the disease transmission coefficients β1,β2,β3 with different rates to their baseline values. The implementation of a real-data set of monkeypox infections makes this study more visible and important within the existing literature.

Acknowledgements

The authors would like to extend their appreciation to the Deanship of Scientific Research at King Khalid University for supporting this work through a research group program under Grant No. R.G.P2/202/44.

Author contributions

B.L. and M.A. improve the language of the manuscript, reviewing and editing, validate governing equations and all mathematical results with care, and project admiration. S.F and S.U. wrote the original manuscript, performed mathematical results and numerical simulations. R.N. and S.W.T. conceptualized the main problem, supervision, formal analysis, and perform data analysis. All authors are agreed on the final draft of the submission file.

Data availability

The data that support the findings of this study are available from the corresponding author up on reasonable request. Further, no experiments on humans and/or the use of human tissue samples involved in this study.

Competing interest

The authors declare no competing interests.

Footnotes

Publisher's note

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Associated Data

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Data Availability Statement

The data that support the findings of this study are available from the corresponding author up on reasonable request. Further, no experiments on humans and/or the use of human tissue samples involved in this study.


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