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. 2026 Jun 8;16:26017. doi: 10.1038/s41598-026-55901-2

A data-driven analysis and forecasting of Leishmaniasis-COVID-19 co-infection model using ensemble Kalman filter

Muhammad Said 1, Mussa A Stephano 2, Il Hyo Jung 1,3,✉
PMCID: PMC13487154  PMID: 42259893

Abstract

Co-infections involving viruses and parasites pose a major concern for global health, particularly in areas where both infections are endemic. In this paper, we present a co-infection epidemic model that considers the transmission dynamics of COVID-19 and leishmaniasis among human and vector populations. The model is developed based on considering the specific latency periods of each infection, treatment, recovery, reinfection, and cross-infection process. The Ensemble Kalman Filter technique is applied to estimate the key model’s parameters using real data, incorporating temporal variation and uncertainty in disease transmission and progression. The model is first divided into COVID-19-only and leishmaniasis-only sub-models to validate the dynamics of each disease over 12 months. For the COVID-19 sub-model, several important estimated parameters include transmission rate Inline graphic, disease mortality Inline graphic, and treatment rate Inline graphic, indicating a relatively slow response to disease treatments and moderate disease severity. On the other hand, the Leishmaniasis model had a slightly lower transmission rate Inline graphic, and a considerably higher treatment rate Inline graphic, implying more efficient case management of the vector-borne disease. The complete model for co-infection, estimated from three groups of six months of data, exhibits synergistic effects through interaction parameters Inline graphic and Inline graphic that reflect a higher likelihood of acquiring another disease while already infected with the first. The model predictions were highly consistent with observed data, and the estimated parameters show significant temporal variability. Projections over a three-month horizon demonstrated strong predictive performance. These results underscore the need for an integrated surveillance and control framework for co-endemic disease management.

Keywords: COVID-19, Leishmaniasis, Co-infection model, EnKF, Forecasting, Parameter estimation, Real data analysis

Subject terms: Computational biology and bioinformatics, Diseases, Mathematics and computing

Introduction

Co-infections by different pathogens are an increasing area of concern, especially in areas where endemic diseases coincide with global pandemics1. Leishmaniasis, caused by protozoan parasites of the genus Leishmania and transmitted by sand-flies, is a neglected tropical disease that affects millions worldwide2. COVID-19, caused by the novel coronavirus SARS-CoV-2, has taken a deep toll on global health systems3,4. While both diseases operate through different biological mechanisms, their geographical overlap in high-disease-burden areas increases the possibility of co-infection, raising important questions about combined effects on the immune system and disease severity in co-infected hosts5.

The biological interaction of Leishmaniasis and COVID-19 co-infection is complex and largely modulated by their contrasting effects on the immune system. Leishmaniasis is characterised by parasitic invasion of macrophages, leading to disruption of immune regulation and resultant chronic inflammation6. COVID-19 causes a hyperactive immune response in severe cases, often leading to a cytokine storm. Co-infection may amplify such immune disturbances, enhancing tissue damage and disease severity. Moreover, immunosuppression due to visceral Leishmaniasis may impede effective immune responses against SARS-CoV-2 and complicate treatment outcomes7.

The co-infection context is further complicated by overlapping biological and environmental risk factors. Conditions prevalent in Leishmaniasis-endemic regions, including malnutrition, poverty, and weakened immunity, may increase vulnerability to severe COVID-198. Furthermore, the sand-fly vector of Leishmaniasis is most common in tropical and subtropical climates, the same regions where COVID-19 has had considerable impact. Understanding the biological consequences of this co-infection is important for informing therapeutic interventions and mitigating the combined health burden9.

The potential impact of co-infection on healthcare systems is substantial. As illustrated in Fig. 1, Leishmaniasis–COVID-19 co-infection involves overlapping transmission pathways, immune impairment, and compounded disease manifestations that can hinder diagnosis, delay treatment, and elevate mortality risk. Co-infected individuals are therefore likely to require more elaborate management approaches, given the interaction of immune responses and the distinct therapies required by each disease10. This adds to the resource burden in areas already constrained by Leishmaniasis management needs. Knowledge of such dynamics is essential for informing public health policies on resource optimisation and integrated disease management11.

Fig. 1.

Fig. 1

Transmission pathways and health effects of Leishmaniasis–COVID-19 co-infection. Sandfly-mediated transmission of Leishmaniasis involves humans and animal reservoirs, resulting in cutaneous and visceral disease manifestations. When combined with COVID-19, overlapping symptoms and immune impairment can hinder diagnosis, delay treatment, and elevate disease burden and fatality risk.

Mathematical modelling plays a fundamental role in understanding, predicting, and controlling the spread of infectious diseases, providing a rigorous quantitative framework for evaluating intervention strategies such as vaccination, treatment, and vector control12–19. In particular, compartmental models incorporating stability analysis, sensitivity evaluation, and optimal control have proven indispensable tools for characterising transmission dynamics across a wide range of pathogens, including dengue, Mpox, hepatitis, and emerging respiratory viruses12–19 Building on this broader methodological foundation, various mathematical models have been developed specifically to study the dynamics of co-infections, offering important insights into how multiple pathogens interact within a shared host population20–25. Teklu and Mekonnen20 developed and analysed a mathematical model of HIV/AIDS and pneumonia co-infection, examining treatment possibilities at each stage of the disease and deriving effective treatment strategies. Said et al.21 performed identifiability analysis of an HIV–Ebola co-infection model using the maximum likelihood estimation method. Amoah-Mensah et al.22 investigated the stability of a mathematical model describing co-infection dynamics between Zika virus and malaria in a malaria-endemic region, advancing our understanding of disease relationships and contributing to preventive strategy development. Said et al.23 formulated and analysed a compartmental leptospirosis–COVID-19 co-infection model fitted to real data, establishing a methodological precedent for the present work. Slater et al.24 utilised a mathematical model to investigate the interaction between malaria and lymphatic filariasis, shedding light on the population-level dynamics of parasitic co-infections. Ringa et al.25 introduced a mathematical model to study the dynamics of HIV and COVID-19 co-infection, analysing transmission dynamics and optimal control strategies.

Despite this growing body of literature, no prior study has developed a compartmental model that jointly captures the transmission dynamics of COVID-19 and Leishmaniasis with explicit human-vector coupling. Furthermore, existing co-infection models rarely employ data assimilation frameworks such as the Ensemble Kalman Filter (EnKF) to estimate time-varying parameters from real epidemiological data. The present work addresses this gap by: (i) formulating a novel ODE-based co-infection model that integrates bidirectional disease interactions, treatment dynamics, and an explicit sandfly vector population; (ii) applying the EnKF to dynamically estimate model parameters from real-world COVID-19 and Leishmaniasis case data; and (iii) performing short-term forecasting with quantified uncertainty. To the best of our knowledge, this is the first data-driven co-infection modelling study combining these two pathogens.

In this work, we present a nonlinear compartmental model based on ordinary differential equations to study the dynamics of COVID-19 and Leishmaniasis co-infection, with explicit modelling of human and sandfly vector populations. A data assimilation framework using the EnKF is applied to estimate time-evolving model parameters from epidemiological data reports. The model is applied to validate single-disease dynamics, quantify co-infection interactions, and make short-term forecasts.

Model formulation

A nonlinear mathematical model based on ordinary differential equations (ODEs) is developed to study the transmission and progression of COVID-19, Leishmaniasis, and their co-infection. The human population compartments are: susceptible individuals (S); exposed to COVID-19 (Inline graphic) or Leishmaniasis (Inline graphic); infectious with COVID-19 (Inline graphic), Leishmaniasis (Inline graphic), or both (Inline graphic); under treatment for COVID-19 (Inline graphic) or Leishmaniasis (Inline graphic); and recovered from each (Inline graphic, Inline graphic). The sandfly vector population includes susceptible (Inline graphic), exposed (Inline graphic), and infectious (Inline graphic) vectors.

The model formulation is grounded in the following explicitly stated biological and epidemiological assumptions:

  1. The human population is stratified into mutually exclusive compartments based on infection status, with homogeneous mixing assumed within the population.

  2. Individuals may contract COVID-19 or Leishmaniasis independently; co-infection is also possible due to overlapping risk factors and immunological vulnerability. This is captured by the bidirectional interaction parameters Inline graphic and Inline graphic.

  3. COVID-19 spreads via human-to-human contact (governed by Inline graphic), whereas Leishmaniasis follows a vector-borne route through infected sandflies (governed by Inline graphic). Human-to-vector transmission is captured by Inline graphic.

  4. Exposed individuals (Inline graphic, Inline graphic) progress to the infectious stage at disease-specific rates, reflecting the incubation periods of each disease.

  5. Co-infected individuals (Inline graphic) experience elevated disease burden and mortality compared to singly infected individuals. The co-infection-induced mortality rate Inline graphic is assumed higher than the single-disease mortality rates Inline graphic and Inline graphic, consistent with clinical evidence of compounded immunological disruption.

  6. Treatment compartments (Inline graphic, Inline graphic) capture the effects of therapeutic intervention. Treated individuals may either recover or die; transition rates are derived from observed clinical dynamics. Lower treatment rates in the co-infection model compared to sub-models reflect possible healthcare access delays or difficulty in distinguishing overlapping symptoms.

  7. Recovery provides temporary immunity within the model’s time frame; recovered individuals (Inline graphic, Inline graphic) may lose immunity at rates Inline graphic and Inline graphic and return to the susceptible class.

  8. The sandfly vector population is modeled with susceptible (Inline graphic), (E_v) exposed, and infected (Inline graphic) compartments; vector infection occurs only through contact with infectious human hosts (Inline graphic and Inline graphic), consistent with Leishmaniasis transmission biology.

The complete model structure is illustrated schematically in Fig. 2, which presents the flowchart of all compartments and transition pathways of the co-infection model, including human-to-human COVID-19 transmission, vector-mediated Leishmaniasis transmission, and bidirectional co-infection interactions. The governing ODE system is given in model (1); parameter descriptions are summarized in Table 1.

graphic file with name d33e591.gif 1

Fig. 2.

Fig. 2

Schematic diagram of the co-infection model. All compartments and transition pathways are shown, including human-to-human COVID-19 transmission (via Inline graphic), vector-mediated Leishmaniasis transmission (via Inline graphic, Inline graphic), bidirectional co-infection enhancement rates (Inline graphic, Inline graphic), treatment flows (Inline graphic, Inline graphic), and recovery pathways (Inline graphic, Inline graphic, Inline graphic, Inline graphic).

Table 1.

Model parameters and their biological interpretations for the Leishmaniasis–COVID-19 co-infection system.

Parameter Biological meaning
Λ Recruitment rate into the human population
μ Natural mortality rate of humans
Inline graphic COVID-19–induced mortality rate
Inline graphic Leishmaniasis-induced mortality rate
Inline graphic Disease-induced mortality rate for co-infected individuals
Inline graphic Mortality rate among individuals under COVID-19 treatment
Inline graphic Mortality rate among individuals under Leishmaniasis treatment
Inline graphic Effective transmission rate of COVID-19 among humans
Inline graphic Transmission rate of Leishmaniasis from infectious vectors to susceptible humans
Inline graphic Rate of acquiring Leishmaniasis by individuals infected with COVID-19
Inline graphic Rate of acquiring COVID-19 by individuals infected with Leishmaniasis
Inline graphic Biting rate of sandflies on susceptible humans
Inline graphic Biting rate of sandflies on Leishmaniasis-infected humans
Inline graphic Progression rate from exposed to infectious COVID-19 class
Inline graphic Progression rate from exposed to infectious Leishmaniasis class
Inline graphic Progression rate from exposed to infectious vector class
Inline graphic Recovery rate of COVID-19-infected individuals
Inline graphic Recovery rate of Leishmaniasis-infected individuals
Inline graphic Recovery rate from COVID-19 for co-infected individuals
Inline graphic Recovery rate from Leishmaniasis for co-infected individuals
Inline graphic Treatment initiation rate for COVID-19-infected individuals
Inline graphic Treatment initiation rate for Leishmaniasis-infected individuals
Inline graphic Recovery rate of individuals treated for COVID-19
Inline graphic Recovery rate of individuals treated for Leishmaniasis
Inline graphic Rate of loss of immunity to COVID-19
Inline graphic Rate of loss of immunity to Leishmaniasis
π Recruitment rate of the sandfly vector population
Inline graphic Transmission rate of Leishmaniasis from infected humans to susceptible vectors
Inline graphic Natural mortality rate of the vector population

Ensemble Kalman filter for parameter estimation

The Ensemble Kalman Filter (EnKF) is a sequential data assimilation technique that combines model predictions with observed data to estimate both the state and parameters of nonlinear systems26,27. Unlike the traditional Kalman Filter, which assumes linear dynamics, or the Extended Kalman Filter, which uses linear approximations, the EnKF employs an ensemble of state realisations to compute error statistics, making it particularly suitable for nonlinear and high-dimensional epidemiological models28–30.

Let the augmented state vector be defined as

graphic file with name d33e864.gif

where the state sub-vector

graphic file with name d33e868.gif

contains all compartmental state variables, and the parameter sub-vector

graphic file with name d33e872.gif

contains all unknown model parameters to be estimated. Here the superscript Inline graphic denotes the vector transpose, indicating that although each sub-vector is written as a row for typographical convenience, it is treated as a column vector in all subsequent matrix operations.

Ensemble initialisation. An ensemble of N = 100 members Inline graphic is initialised. Each state variable is initialised from a distribution consistent with reported epidemiological data at t = 0 (e.g. reported case counts for Inline graphic, Inline graphic, Inline graphic, with the susceptible pool inferred from the total population). Unknown parameters are initialised from uniform distributions over biologically plausible ranges: e.g. Inline graphic; Inline graphic; Inline graphic.

Forecast step. At each time step k, each ensemble member is propagated forward using the model dynamics:

graphic file with name d33e928.gif

where Inline graphic is the model operator and Inline graphic denotes process noise. Process noise is injected into the parameter components at each step to prevent ensemble collapse and allow parameters to evolve over time; the process noise covariance Inline graphic is diagonal with small variance for each parameter.

Observation function. Predicted observations for each ensemble member are computed as:

graphic file with name d33e948.gif

where Inline graphic maps the augmented state to the observable quantities, i.e. the monthly reported case counts for Inline graphic, Inline graphic, and Inline graphic. Observation noise Inline graphic is assumed Gaussian with zero mean and covariance Inline graphic, where the standard deviations are set proportional to the observed case counts to reflect reporting uncertainty.

Analysis step. The ensemble means are

graphic file with name d33e981.gif

The cross-covariance and observation covariance are

graphic file with name d33e985.gif
graphic file with name d33e988.gif

The Kalman gain matrix is

graphic file with name d33e992.gif

Finally, each ensemble member is updated using the actual observation Inline graphic:

graphic file with name d33e1001.gif

This procedure is repeated iteratively at each monthly observation time-point, enabling joint estimation of state trajectories and time-varying parameters.

Results

This section presents simulation results for the COVID-19-only sub-model, the Leishmaniasis-only sub-model, and the full co-infection model. Individual sub-model simulations were run over 12 months; the co-infection model was fitted to three independent 6-month datasets. The EnKF was applied throughout for parameter estimation and state updating. Mean parameter values are reported in Tables 2, 3 and 4.

Table 2.

Values of model parameters with units and sources.

Parameter Value Unit Source
Λ – Inline graphic Estimated31,32
μ – Inline graphic Estimated33
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic – Inline graphic Estimated (fitting)
Inline graphic 0.8600 Inline graphic 34
Inline graphic 0.7000 Inline graphic 35
Inline graphic 0.0300 Inline graphic 35
Inline graphic 0.0100 Inline graphic 36
Inline graphic 0.0100 Inline graphic 36
Inline graphic 0.0019 Inline graphic 23
Inline graphic 0.0022 Inline graphic 23
Inline graphic 0.0059 Inline graphic 37
Inline graphic 0.0250 Inline graphic 35
Inline graphic 0.9629 Inline graphic 38
Inline graphic 0.0064 Inline graphic 39
π 8.2300 Inline graphic 35
Inline graphic 0.0100 Inline graphic 35

Table 3.

Estimated parameter values for the COVID-19 and Leishmaniasis sub-models using two different 12-month datasets.

Parameter Estimated value C.I
COVID-19 Inline graphic 0.2451 (0.2193-0.3134)
Inline graphic 0.0067 (0.0015-0.0324)
Inline graphic 0.0142 (0.0097-0.0782)
Inline graphic 0.0075 (0.0016-0.0120)
Inline graphic 0.0714 (0.0539-0.0916)
Leishmaniasis Inline graphic 0.2319 (0.1039-0.3521)
Inline graphic 0.0041 (0.0011-0.0210)
Inline graphic 0.0721 (0.0021-0.0976)
Inline graphic 0.0013 (0.0009-0.0109)
Inline graphic 0.0613 (0.0413-0.0896)
Inline graphic 0.0004 (0.0001-0.0007)

Table 4.

Model parameter estimates using three different observational 6-month datasets.

Parameter Estimated value C.I
COVID-19 Inline graphic 0.2806 (0.2193-0.3134)
Inline graphic 0.0031 (0.0015-0.0324)
Inline graphic 0.0643 (0.0097-0.0782)
Inline graphic 0.0045 (0.0016-0.0120)
Leishmaniasis Inline graphic 0.2204 (0.1039-0.3521)
Inline graphic 0.0033 (0.0011-0.0210)
Inline graphic 0.0380 (0.0021-0.0976)
Inline graphic 0.0012 (0.0009-0.0109)
Co-infection Inline graphic 0.3624 (0.3124-0.4312)
Inline graphic 0.3394 (0.3013-0.4127)
Inline graphic 0.0060 (0.0050-0.0070)

In the COVID-19-only sub-model, the EnKF estimated a transmission rate Inline graphic, consistent with community-level SARS-CoV-2 transmission in similar settings and reflecting the airborne nature of the pathogen. The disease-induced mortality rate Inline graphic reflects a measurable mortality burden among untreated individuals, consistent with reported COVID-19 case-fatality rates in resource-limited settings. The treatment initiation rate Inline graphic is relatively low, suggesting possible delays or limitations in healthcare access or diagnosis. The death rate among treated individuals, Inline graphic, is slightly higher than Inline graphic, which may reflect late-stage treatment initiation or comorbidities. The recovery rate of treated individuals, Inline graphic, indicates a positive therapeutic response: patients under clinical care are substantially more likely to recover than to die. Temporal evolution of these parameters is illustrated in Figs. 3, 4, 5 and 6.

Fig. 3.

Fig. 3

Model fitting of COVID-19 data using the Ensemble Kalman Filter (EnKF) approach. The observed data points are shown alongside the model predictions, with the shaded region representing the 95% confidence interval. The EnKF enables real-time parameter estimation and state correction, capturing the stochastic variability in disease progression.

Fig. 4.

Fig. 4

Monthly variation in estimated parameters Inline graphic, and Inline graphic, over a 12-month period.

Fig. 5.

Fig. 5

Monthly variation in estimated parameters Inline graphic, and Inline graphic over a 12-month period.

Fig. 6.

Fig. 6

Monthly variation in estimated parameter Inline graphic over a 12-month period.

In the Leishmaniasis-only sub-model, the estimated transmission rate Inline graphic reflects a sustained but moderate disease spread, consistent with the vector-dependent nature of Leishmaniasis. The disease-induced mortality rate for untreated individuals, Inline graphic, is lower than that of COVID-19, likely reflecting a more chronic and slower-progressing disease course. The higher treatment rate Inline graphic suggests better case detection or treatment compliance for Leishmaniasis in the studied population compared to COVID-19. The very low mortality among treated individuals, Inline graphic, highlights the efficacy of available antileishmanial therapies. The recovery rate Inline graphic confirms favourable clinical outcomes under treatment. The estimated human-to-vector transmission rate, Inline graphic, is very low, reflecting ecological constraints on sandfly infection. Temporal parameter trends are illustrated in Figs. 7, 8, 9 and 10.

Fig. 7.

Fig. 7

Model fitting of Leishmaniasis data using the Ensemble Kalman Filter (EnKF) approach. The observed data points are shown alongside the model predictions, with the shaded region representing the 95% confidence interval.

Fig. 8.

Fig. 8

Monthly variation in estimated parameters Inline graphic, Inline graphic over a 12-month period.

Fig. 9.

Fig. 9

Monthly variation in estimated parameters Inline graphic, and Inline graphic. over a 12-month period.

Fig. 10.

Fig. 10

Monthly variation in estimated parameters Inline graphic, and Inline graphic over a 12-month period.

The parameter estimation for the full co-infection model reveals important insights into the joint disease dynamics. The COVID-19 transmission rate was estimated at Inline graphic, slightly elevated compared to the sub-model, possibly reflecting increased host susceptibility or behavioural mixing under co-infection conditions. For Leishmaniasis, Inline graphic, slightly reduced, which may reflect reporting effects or interaction-induced suppression.

The interaction parameters Inline graphic and Inline graphic quantify the bidirectional synergy of co-infection. Specifically, Inline graphic represents the elevated rate at which COVID-19-infected individuals acquire Leishmaniasis: SARS-CoV-2 causes profound immune dysregulation (cytokine storms, lymphopenia) that reduces the host’s ability to control Leishmania infection. Conversely, Inline graphic represents the elevated risk of COVID-19 acquisition for Leishmaniasis-infected individuals, driven by the macrophage-mediated immunosuppression characteristic of visceral Leishmaniasis, which impairs innate antiviral defences. Both values (Inline graphic) are substantially higher than the primary transmission rates (Inline graphic), confirming that co-infection significantly amplifies transmission risk for both pathogens. The co-infection-induced mortality rate Inline graphic is higher than either single-disease mortality rate, underscoring the compounded health risk for co-infected individuals.

Data fitting results across the three datasets are shown in Figs. 11, 12 and 13, demonstrating strong agreement between model predictions and observed case counts. Parameter evolution plots (Figs. 14, 15, 16, 17 and 18) confirm temporally heterogeneous dynamics. Ensemble heat-maps (Figs. 19, 20, 21, 22 and 23) show progressive narrowing of the ensemble spread, indicating improved parameter confidence as data are assimilated. Three-month forecasts are shown in Figs. 24, 25 and 26; widening confidence intervals in the forecast period are expected and reflect the absence of new observational data.

Fig. 11.

Fig. 11

Model fitting of the COVID-19 infectious population Inline graphic over a six-month period using the Ensemble Kalman Filter (EnKF). The black curve represents the mean prediction from the EnKF based on the evolving ensemble of system states. The blue shaded region denotes the 95% confidence interval, capturing uncertainty in the model estimates. Triangle markers correspond to the observed data points used for data assimilation. The results demonstrate the EnKF’s effectiveness in capturing the temporal trends of the COVID-19 epidemic under uncertainty.

Fig. 12.

Fig. 12

Model fitting of the Leishmaniasis infectious population Inline graphic over a six-month period using the Ensemble Kalman Filter (EnKF). The mean EnKF prediction is shown as a black curve, while the 95% confidence interval is illustrated with a blue shaded region. Observed case data are represented by triangle markers. This figure highlights the EnKF’s ability to assimilate noisy data and produce a probabilistic estimate of disease progression for a neglected tropical disease.

Fig. 13.

Fig. 13

Model fitting of the co-infected population Inline graphic (individuals simultaneously infected with both COVID-19 and Leishmaniasis) over six months using the Ensemble Kalman Filter (EnKF). The black line indicates the EnKF mean estimate, while the surrounding blue shaded region represents the 95% confidence interval. Observational data points are shown as triangle markers. The results illustrate the EnKF’s capacity to capture the interactions between co-circulating infections and infer latent epidemic behavior under uncertainty.

Fig. 14.

Fig. 14

Monthly variation in estimated parameters Inline graphic, and Inline graphic over a 6-month period.

Fig. 15.

Fig. 15

Monthly variation in estimated parameters Inline graphic, and Inline graphic over a 6-month period.

Fig. 16.

Fig. 16

Monthly variation in estimated parameters Inline graphic, and Inline graphic over a 6-month period.

Fig. 17.

Fig. 17

Monthly variation in estimated parameters Inline graphic, and Inline graphic over a 6-month period.

Fig. 18.

Fig. 18

Monthly variation in estimated parameters Inline graphic, Inline graphic, and Inline graphic over a 6-month period.

Fig. 19.

Fig. 19

Heat-map visualization of the temporal evolution and ensemble diversity for each estimated parameter (Inline graphic and Inline graphic) across all time steps. Each subplot corresponds to a specific parameter and displays its values for 100 ensemble members over 6 months. Color intensity indicates the magnitude of the parameter estimates. This confirms parameter variability and dynamic tracking throughout the Ensemble Kalman Filter process.

Fig. 20.

Fig. 20

Heat-map visualization of the temporal evolution and ensemble diversity for each estimated parameter (Inline graphic and Inline graphic) across all time steps. Each subplot corresponds to a specific parameter and displays its values for 100 ensemble members over 6 months. Color intensity indicates the magnitude of the parameter estimates. This confirms parameter variability and dynamic tracking throughout the Ensemble Kalman Filter process.

Fig. 21.

Fig. 21

Heat-map visualization of the temporal evolution and ensemble diversity for each estimated parameter (Inline graphic and Inline graphic) across all time steps. Each subplot corresponds to a specific parameter and displays its values for 100 ensemble members over 6 months. Color intensity indicates the magnitude of the parameter estimates. This confirms parameter variability and dynamic tracking throughout the Ensemble Kalman Filter process.

Fig. 22.

Fig. 22

Heat-map visualization of the temporal evolution and ensemble diversity for each estimated parameter (Inline graphic and Inline graphic) across all time steps. Each subplot corresponds to a specific parameter and displays its values for 100 ensemble members over 6 months. Color intensity indicates the magnitude of the parameter estimates. This confirms parameters variability and dynamic tracking throughout the Ensemble Kalman Filter process.

Fig. 23.

Fig. 23

Heat-map visualization of the temporal evolution and ensemble diversity for each estimated parameter (Inline graphic, Inline graphic and Inline graphic) across all time steps. Each subplot corresponds to a specific parameter and displays its values for 100 ensemble members over 6 months. Color intensity indicates the magnitude of the parameter estimates. This confirms parameter variability and dynamic tracking throughout the Ensemble Kalman Filter process.

Fig. 24.

Fig. 24

Three-month ahead forecast of COVID-19 (Inline graphic) cases using the Ensemble Kalman Filter (EnKF). The plot shows fitted values during the observed period and projected values with 95% confidence intervals beyond the fitting horizon.

Fig. 25.

Fig. 25

Three-month ahead forecast of Leishmaniasis (Inline graphic) cases using the EnKF-based model. The shaded region indicates the 95% confidence interval of the forecasted values.

Fig. 26.

Fig. 26

Forecast of co-infection (Inline graphic) cases for the next three months. The plot displays both historical fit and predictive mean with confidence bounds, highlighting the expected dynamics under current parameter estimates.

Discussion

The simulation results offer important insights into the transmission dynamics of COVID-19 and Leishmaniasis, both individually and as a co-infection system. The application of the EnKF enabled dynamic estimation of key epidemiological parameters while accounting for uncertainty in real data. Individual sub-model validation over 12 months provided a solid foundation for the co-infection analysis. The strong agreement between observations and predictions confirms the model structure and estimation framework.

In the COVID-19 sub-model, the estimated Inline graphic is consistent with community-level SARS-CoV-2 spread. The relatively slow treatment initiation rate (Inline graphic) may reflect diagnostic delays or healthcare access barriers. In contrast, the The leishmaniasis sub-model showed a higher treatment rate (Inline graphic), suggesting a more efficient clinical response to this disease in the modelled setting. The lower mortality among Leishmaniasis-treated individuals (Inline graphic) highlight effective antileishmanial therapy. These differences reflect fundamentally distinct transmission mechanisms and disease management realities: COVID-19 requires rapid response to prevent large-scale community outbreaks, while Leishmaniasis control relies more heavily on vector control and sustained treatment access.

The co-infection analysis revealed that the simultaneous presence of both diseases significantly alters transmission and clinical dynamics. The elevated Inline graphic in the co-infection model may reflect heightened susceptibility due to immunosuppression, while the slightly lower Inline graphic may result from under-reporting or interaction-induced suppression of Leishmaniasis spread. The high values of Inline graphic and Inline graphic confirm a strong bidirectional synergy. The higher co-infection mortality rate (Inline graphic) compared to single-disease rates underscores the compounded clinical risk.

These findings carry several important implications for public health practice. First, the high values of the interaction parameters (Inline graphic) indicate that in co-endemic settings, the presence of either disease substantially elevates the risk of the other. This calls for integrated co-infection surveillance systems capable of simultaneously tracking and reporting both diseases and flagging at-risk individuals. Second, resource allocation strategies in Leishmaniasis-endemic regions must account for the potential for COVID-19 co-infection, which may require additional clinical resources (intensive care, combined diagnostic protocols). Third, the higher mortality in co-infected individuals argues for prioritising this group in triage and treatment protocols. Fourth, the success of the EnKF framework in dynamically tracking parameter changes demonstrates its value for real-time epidemic monitoring; health authorities could use such adaptive models to update disease projections as new surveillance data becomes available. Finally, the differing treatment dynamics between the two diseases (faster uptake for Leishmaniasis, slower for COVID-19) suggest that different intervention priorities are needed: COVID-19 management should emphasise early detection and rapid clinical referral, while Leishmaniasis control should maintain strong vector control programmes and sustained access to antileishmanial therapies.

Conclusion

This study presents a comprehensive modelling framework to analyse the transmission dynamics of COVID-19 and Leishmaniasis, both individually and as a co-infection system, using the Ensemble Kalman Filter for dynamic parameter estimation. Sub-model simulations provided a clear epidemiological characterisation of each disease, while the co-infection model revealed critical interaction effects that alter transmission rates and clinical outcomes. The quantitative agreement between model projections and observed data confirms both the model structure and the capacity of the EnKF to infer time-varying disease dynamics from real-world data.

Significant differences in transmission mechanisms, mortality rates, and treatment dynamics were identified between the two diseases. COVID-19’s direct human-to-human transmission and low treatment uptake necessitate rapid response interventions, while Leishmaniasis’ vector-borne nature and favourable treatment outcomes underscore the importance of persistent vector control and treatment access. Under co-infection, the bidirectional interaction parameters Inline graphic and Inline graphic indicate significant mutual amplification of transmission risk and mortality, requiring comprehensive clinical management.

The findings underscore the importance of integrated disease surveillance in co-endemic regions, and the successful application of the EnKF demonstrates the value of adaptive data assimilation for real-time epidemic monitoring. These insights contribute to a more nuanced understanding of multi-pathogen epidemics and can inform holistic public health responses and resource allocation policies.

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIT) (No. RS-2024-00342113 and RS-2022-NR070839).

Author contributions

M.S. (Muhammad Said) conceived the study, developed the mathematical model, implemented the Ensemble Kalman Filter (EnKF) algorithm, performed the formal analysis and numerical simulations, and drafted the original manuscript. M.A.S. (Mussa A. Stephano) contributed to data collection, model validation, interpretation of results, and assisted in manuscript preparation and revision. I.H.J. (Il Hyo Jung) supervised the research, contributed to conceptual refinement and methodological design, and critically revised the manuscript for important intellectual content. All authors reviewed the manuscript and approved the final version.

Funding

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIT) (No. RS-2024-00342113 and RS-2022-NR070839).

Data availability

The data used in this study consist of aggregated, publicly available epidemiological records. COVID-19 case data were obtained from the online database https://www.coronaboard.com . Leishmaniasis-related data were derived from aggregated epidemiological records reported in Hashemi et al., An eco-epidemiological study of cutaneous leishmaniasis in Dezful, Iran, during 2004–2011, published in the Journal of Occupational Health and Epidemiology and accessible via the DOI https://doi.org/10.18869/acadpub.johe.3.1.45 . No individual-level or identifiable human data were used in this study.

Declarations

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

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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 used in this study consist of aggregated, publicly available epidemiological records. COVID-19 case data were obtained from the online database https://www.coronaboard.com . Leishmaniasis-related data were derived from aggregated epidemiological records reported in Hashemi et al., An eco-epidemiological study of cutaneous leishmaniasis in Dezful, Iran, during 2004–2011, published in the Journal of Occupational Health and Epidemiology and accessible via the DOI https://doi.org/10.18869/acadpub.johe.3.1.45 . No individual-level or identifiable human data were used in this study.


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