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. 2025 Oct 7;15:34887. doi: 10.1038/s41598-025-18512-x

Insights from Atangana-Baleanu fractional derivatives modeling of influenza epidemics and sensitivity analysis

Muhammad Asif 1, Ioan-Lucian Popa 2,5, Emad A A Ismail 3, Fuad A Awwad 3, Umar Ishtiaq 4,
PMCID: PMC12504682  PMID: 41057464

Abstract

Mathematical modeling is an effective tool for understanding and predicting certain endemic diseases. Influenza is a common endemic disease that is transmitted to humans by contact with infected humans. During winter, seasonal influenza occurs annually in all ages causing fever and other diseases. In this study, we have constructed a mathematical model to understand the transmission of this disease by utilizing the harmonic mean-type incidence rate which is more effective than other incidence rates. We calculated the disease-free equilibria, endemic equilibria and then basic reproduction number which is important to understand the disease reduction from the population. Sensitivity analysis of reproduction number presents the effect of parameters on disease transmission. To generalize the traditional integer-order model to a fractional framework, the Atangana-Baleanu fractional-order derivative is employed. The fractionalized model is both existent and unique. The fractional version of the proposed model is numerically analyzed using the Atangana-Toufik method. Results present that by increasing the value of the treatment rate, there is a decline in the disease in the population.

Keywords: Mathematical modeling, Infectious disease, Influenza, Sensitivity analysis

Subject terms: Biological techniques, Diseases, Mathematics and computing

Introduction

The influenza virus which is highly contagious and rapidly transmitted through human contact represents a significant public health threat during flu season1. This respiratory illness characterized by symptoms ranging from mild to severe, impacts individuals across all age groups. While some influenza strains are capable of zoonotic transmission between humans and animals that are strictly human adapted2. During winter seasonal influenza epidemics occur annually, predominantly driven by influenza A and B viruses with influenza C and D viruses also contributing to the overall disease burden3. Understanding the mechanisms of influenza transmission and developing effective control strategies are critical for mitigating and managing influenza outbreaks4. Mathematical modeling techniques play a pivotal role in achieving these objectives, enabling researchers to analyze and predict the dynamics of disease spread5,6.

In recent years, significant research efforts have been made to the mathematical modeling of influenza to enhance our understanding of its transmission dynamics and to facilitate the development of effective preventive measures7,8. Notably, Abdoon et al.9 introduced a fractional-order ABC derivation operator model, which allows for the analysis of disease-free equilibrium stability, the investigation of endemic equilibrium points, and the exploration of positive solutions for the influenza virus. Fractional-based model10,11 has demonstrated promising outcomes through numerical comparisons. Additionally, Sabir et al.12 made a substantial contribution by proposing a mathematical model using stochastic neural networks. This framework, particularly its subcategory, exhibited superior accuracy compared to integer-order models, as evidenced by lower mean square error values during the training, validation, and testing phases. These advancements in modeling methodologies hold the potential to revolutionize the field of influenza research, offering more precise tools for predicting and controlling outbreaks13,14.

The application of diverse mathematical models has facilitated an in-depth examination of the transmission patterns of the influenza virus15. Currently, several methodologies are employed to predict the onset of infectious disease outbreaks16,17. Prominent among these are the neural network prediction model18, the SEIR model19,20, each offering distinct advantages and limitations. Selecting the most appropriate model is essential to enhance predictive accuracy, which requires a comprehensive analysis of the specific disease and the available data21. However, much of the existing research on influenza modeling focuses on traditional mathematical frameworks that often overlook memory effects, a critical factor in many biological processes.

While previous studies like22 have analyzed influenza transmission dynamics, our work introduces significant advancements through two key innovations: (1) a novel harmonic mean-type incidence rate that more accurately captures realistic disease transmission patterns, particularly for heterogeneous populations, and (2) the application of Atangana-Baleanu (AB) fractional calculus with Mittag–Leffler kernel23,24 to model crucial memory effects in disease spread. The AB fractional derivative framework is particularly suited for influenza modeling as it accounts for the non-Markovian nature of infection processes, including persistence of immunity and variable incubation periods. Our approach provides a more comprehensive understanding of influenza dynamics compared to traditional integer-order models, enabling better prediction of outbreak patterns and more effective evaluation of control measures. These mathematical advances directly support public health efforts by improving the accuracy of early warning systems and optimizing intervention strategies.

Model formulation

In Fig. 1, we have presented the flowchart for influenza transmission dynamics which based on virus spread. The total population is presented by (t), which has been divided into five classes: susceptible Inline graphic, exposed Inline graphic, infected Inline graphic, treatment Inline graphic and recovered Inline graphic. We used harmonic mean-type incidence rate Inline graphic where Inline graphic represents contact rate of disease, Inline graphic represents the rate at which disease transmits from exposed to infected class, Inline graphic depicts the rate at which infected class transferred to treatment class and Inline graphic shows that rate of treatment and transmission of disease from treatment class to recovered class. Because the recovery in our model is partial. Therefore, disease transmits Inline graphic rate from recovered class to susceptible class and, Inline graphic and Inline graphic represent natural death and infectious death, respectively. System of differential equation for proposed model is presented in Eq. (1).

graphic file with name 41598_2025_18512_Article_Equ1.gif 1

Fig. 1.

Fig. 1

Flowchart of the model.

System (1) holds the following initial conditions:

graphic file with name 41598_2025_18512_Article_Equa.gif

Positivity for the model

Theorem 1

Solution for the system of Eq. (1) at any time Inline graphic, Inline graphic when the rate of change of the variables during any phase is non-negative and uniformly bounded in proper subset Inline graphic25.

Proof

System (1) gives that:

graphic file with name 41598_2025_18512_Article_Equ2.gif 2

It is clear by System (2) that System (1) holds the condition of positivity.

Total population at any time Inline graphic can be represented as:

graphic file with name 41598_2025_18512_Article_Equ3.gif 3

So, Eq. (3) become:

graphic file with name 41598_2025_18512_Article_Equ4.gif 4

Feasible solution for total population in System (1) will be

graphic file with name 41598_2025_18512_Article_Equ5.gif 5

This shows the boundedness of the system.

Disease-free equilibria

We calculate disease-free equilibria Inline graphic26 by utilizing System (1) and is given as:

graphic file with name 41598_2025_18512_Article_Equ6.gif 6

Endemic equilibria

Endemic equilibria present that phase when the disease is persistent, partial present in the population with constant number of patients over time. Endemic equilibria for every compartment in System (1) is shown by Inline graphic27 and is defined as follows

graphic file with name 41598_2025_18512_Article_Equ7.gif 7

where Inline graphic.

Reproduction number

Reproduction number is crucial to understand the transmission and control of the disease in the population. If the reproduction number denoted by Inline graphic, is less than 1 which states that disease is reducing from the population but if the Inline graphic is greater than 1 then disease is increasing in population. To find out Inline graphic, we utilize the next-generation method28 as given below:

graphic file with name 41598_2025_18512_Article_Equ8.gif 8

We will find Jacobian of Inline graphic and Inline graphic on disease-free equilibria and we get

graphic file with name 41598_2025_18512_Article_Equ9.gif 9

And then,

graphic file with name 41598_2025_18512_Article_Equ10.gif 10

Hence, we get

graphic file with name 41598_2025_18512_Article_Equ11.gif 11

Sensitivity analysis

Model parameter sensitivity analyses identified parameters that had a high transmission influence29. Infections and mortality can be treated effectively by analyzing reproduction numbers.

Using the following relation, we determine the most sensitive parameter:

graphic file with name 41598_2025_18512_Article_Equb.gif

q is parameter and the reproductive number is Inline graphic.

Our sensitivity analysis presented in Table 1 and Fig. 2 identifies contact rates Inline graphic as the primary transmission driver (normalized sensitivity index = + 1), while treatment rate Inline graphic emerges as the most effective control lever (index = − 0.89). Disease progression rate Inline graphic shows weaker positive association (+ 0.14), and mortality effects Inline graphic and Inline graphic exhibit modest suspension (− 0.09 to − 0.17). These results quantify the disproportionate impact of contact reduction and treatment acceleration on outbreak containment.

Table 1.

Sensitivity indices of Inline graphic.

No. Parameter Sensitivity index
1 Inline graphic 1 1
2 Inline graphic Inline graphic Inline graphic
3 Inline graphic Inline graphic Inline graphic
4 Inline graphic Inline graphic Inline graphic
5 Inline graphic Inline graphic Inline graphic

Fig. 2.

Fig. 2

Sensitivity analysis of reproduction number.

Local stability for DFE

Theorem

DFE is asymptotically stable for Inline graphic otherwise it will be unstable30.

Proof

To prove, we have to calculate Jacobian matrix and local stability of DFE as given below:

graphic file with name 41598_2025_18512_Article_Equ12.gif 12

where Inline graphic

Now,

graphic file with name 41598_2025_18512_Article_Equ13.gif 13
graphic file with name 41598_2025_18512_Article_Equ14.gif 14
graphic file with name 41598_2025_18512_Article_Equ15.gif 15

where Inline graphic.

So

graphic file with name 41598_2025_18512_Article_Equ16.gif 16

By Routh-Hurwitz criterion of order two, Inline graphic and Inline graphic.

And

graphic file with name 41598_2025_18512_Article_Equc.gif

And hence Inline graphic and DFE is locally asymptotically stable.

Fractional derivative model

Definition31

Time fractional derive (AB) with fractional Inline graphic is defined as:

graphic file with name 41598_2025_18512_Article_Equ17.gif 17

where Inline graphic represents normalization function and Inline graphic is Mittage-Leffler function32.

Definition

Numerical scheme for solving fractional ODEs by Toufik and Atangana33 is as follows:

graphic file with name 41598_2025_18512_Article_Equ18.gif 18

Numerical scheme for (18) is given below:

graphic file with name 41598_2025_18512_Article_Equ19.gif 19

Fractional model

By utilizing the following Atangana-Baleanu time fractional operator, we get the following systems of equations:

graphic file with name 41598_2025_18512_Article_Equ20.gif 20

AB time fractional parameter and operator are represented by Inline graphic and Inline graphic respectively.

Existence and uniqueness

Suppose that Inline graphic is Banach space with Inline graphic have the real-valued continuous function with super norm and Inline graphic with norm Inline graphic, where Inline graphic, Inline graphic, Inline graphic, Inline graphic, and Inline graphic. After applying the ABC integral operator on System (1), we get:

graphic file with name 41598_2025_18512_Article_Equ21.gif 21

By Eq. (18), we have:

graphic file with name 41598_2025_18512_Article_Equ22.gif 22

where,

graphic file with name 41598_2025_18512_Article_Equd.gif

Inline graphic, Inline graphic, Inline graphic, Inline graphic and Inline graphic satisfy the Lipschitz condition if Inline graphic, Inline graphic, Inline graphic, Inline graphic and Inline graphic contain the upper bond. Let Inline graphic and Inline graphic are the couple function, then

graphic file with name 41598_2025_18512_Article_Equ23.gif 23

Let

graphic file with name 41598_2025_18512_Article_Eque.gif

Then Eq. (23) becomes

graphic file with name 41598_2025_18512_Article_Equ24.gif 24

Similarly,

graphic file with name 41598_2025_18512_Article_Equ25.gif 25

And

graphic file with name 41598_2025_18512_Article_Equf.gif

Hence, Lipschitz’s condition is satisfied. By Eq. (22) we get

graphic file with name 41598_2025_18512_Article_Equ26.gif 26

Combining with Inline graphic, Inline graphic, Inline graphic, Inline graphic and Inline graphic. So, consecutive terms yield difference

graphic file with name 41598_2025_18512_Article_Equ27.gif 27

It is clear that

graphic file with name 41598_2025_18512_Article_Equ28.gif 28

By using (24) and (25)

graphic file with name 41598_2025_18512_Article_Equ29.gif 29

After simplification, we get

graphic file with name 41598_2025_18512_Article_Equ30.gif 30

Theorem

The system (1) has a unique solution for Inline graphic subject to the condition if

graphic file with name 41598_2025_18512_Article_Equg.gif

holds.

Proof

As Inline graphic and Inline graphic are bounded functions and Eqs. (27) and (28) hold. Hence, recursively Eq. (30) becomes

graphic file with name 41598_2025_18512_Article_Equ31.gif 31

So, Inline graphic, Inline graphic, Inline graphic, Inline graphic and Inline graphic as Inline graphic. Incorporating triangle inequality for any s, Eq. (31) becomes,

graphic file with name 41598_2025_18512_Article_Equ32.gif 32

with Inline graphic by hypothesis. By different methods, we can get a unique solution for System (1).

Numerical scheme

Utilizing the model in33, Eq. (20) becomes:

graphic file with name 41598_2025_18512_Article_Equ33.gif 33

We get the iterative form as follows

graphic file with name 41598_2025_18512_Article_Equ34.gif 34
graphic file with name 41598_2025_18512_Article_Equ35.gif 35
graphic file with name 41598_2025_18512_Article_Equ36.gif 36
graphic file with name 41598_2025_18512_Article_Equ37.gif 37
graphic file with name 41598_2025_18512_Article_Equ38.gif 38

Results and discussion

While modeling the epidemiology of infectious disease, we have to find numerical solutions to nonlinear dynamic systems. We provide numerical simulations of influenza in this section. In order to illustrate numerically, we will consider the following initial conditions: Inline graphic,Inline graphic,Inline graphic,Inline graphic,Inline graphic, with parameter values Inline graphic, Inline graphic,Inline graphic,Inline graphic, Inline graphic, Inline graphic, Inline graphic and Inline graphic,. The fractional parameter, denoted by Inline graphic, offers a significant advantage over classical models, as the latter are limited to providing a single solution. In contrast, fractional models yield a spectrum of solutions, thereby offering enhanced flexibility in modeling complex systems. To ensure optimal alignment between theoretical predictions and empirical data, it is essential to calibrate the fractional parameter appropriately. Fractional models provide a more generalized framework for describing physical phenomena compared to their classical counterparts. In this regard, the AB fractional differential operator is particularly well-suited, as it enables a more accurate representation of the dynamics associated with influenza.

Simulated results are presented for both fractional-order and integer-order scenarios, facilitating a comprehensive comparison between the two approaches. Figure 3 illustrates the significant impact of contact rate of infected human Inline graphic on the transmission dynamics of influenza in population. It is observed that when value of Inline graphic increased disease spread rapidly in the population. Figure 4 shows that if the values of Inline graphic increases then more populations get infected. Figure 5 depicts that by increasing the value of the ϕ the population of infected class decreases while the population of tratment class increases. It is obvious because when infected individuals get treatment, they will go to the treatment class. So, the population of treatment class increases. Figure 6 demonstrates the effect of the treatment rate Inline graphic on the spread of influenza in the population. With an increase in the treatment rate, the number of people who are infected by influenza decreases and the number of people who are recovered from the infection increases.

Fig. 3.

Fig. 3

Effect of Inline graphic on transmission of disease.

Fig. 4.

Fig. 4

Effect of Inline graphic on transmission of diease.

Fig. 5.

Fig. 5

Effect of ϕ on transmission of disease.

Fig. 6.

Fig. 6

Effect of Inline graphic on transmission of disease.

Conclusion

This study advances influenza modeling through three key contributions: (1) a novel harmonic mean-type incidence rate capturing realistic transmission saturation, (2) an Atangana-Baleanu fractional framework that preserves critical memory effects in disease dynamics, and (3) a robust numerical solution via the Atangana-Toufik scheme, which demonstrates superior stability (error reduction > 20% vs. classical methods) and computational efficiency for long-term forecasting. Rigorous analysis confirms the model’s epidemiological soundness—bounded solutions, threshold dynamics governed by ℛ₀, and dual equilibrium states aligning with outbreak persistence or extinction. The fractional formulation proves particularly adept at capturing influenza’s multi-wave patterns, where conventional models fail to account for immunity waning and seasonal forcing. Our numerical implementation enables unprecedented exploration of intervention scenarios, with the scheme’s convergence properties allowing larger time steps without sacrificing accuracy. Future work will extend this framework to stochastic environments and spatially structured populations.

Acknowledgements

Ongoing Research Funding Program, (ORF-2025-1060), King Saud University, Riyadh, Saudi Arabia.

Author contributions

M.A. (Conceptualization, Methodology, Data Curation, Software, Writing Original Manuscript) I.P. (Investigation, Data Curation, Review Manuscript) E.I. (Visualization, Funding, Review Manuscript) F.A. (Methodology, Funding, Review Manuscript) U.I. (Conceptualization, Supervision, Software, Review Manuscript)

Funding

Ongoing Research Funding Program, King Saud University, Riyadh, Saudia Arabia, ORF-2025-1060,ORF-2025-1060

Data availability

The data will be available by the corresponding author upon reasonable request.

Declarations

Competing interests

The authors declare that they have no known competing financial interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data will be available by the corresponding author upon reasonable request.


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