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Infectious Disease Modelling

Elsevier BV

Preprints posted in the last 90 days, ranked by how well they match Infectious Disease Modelling's content profile, based on 54 papers previously published here. The average preprint has a 0.05% match score for this journal, so anything above that is already an above-average fit.

1
A New Method to Predict the Effect of an Intervention in the Host Population to Reduce the Magnitude of an Outbreak of a Vector-Borne Infection

Coutinho, F. A. B.; Amaku, M.; Kallas, E. G.; Massad, E.

2026-07-19 epidemiology 10.64898/2026.07.16.26358272 medRxiv
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In this paper, we propose a new model to estimate the impact of an intervention on human hosts of a vector-borne infection, such as dengue, which occurs in yearly outbreaks of different magnitudes. The model applies to these outbreaks and, in fact, is independent of their intensity, that is, it does not require the steady-state assumption. The model takes as input the officially reported age-dependent number of cases of a vector-borne infection. It is deterministic and does not account for stochasticity. Our objective is to estimate the impact of the intervention (the efficacy), and we rely on the observed fact that the age distribution of the proportion of cases of the infections transmitted by the same vector is independent of both the intensity of transmission and the geographic area studied, at least for Brazilian regions. This finding is highlighted in the main text and forms the basis of our calculations. A hypothetical intervention is simulated using a dengue vaccine, which allows the determination of the optimal strategy for a vaccination campaign.

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The Immunity Paradox of Bed Nets: Why Reducing Exposure Can Still Strengthen Malaria Control

Tasse, A. J. O.; Ghakanyuy, B. M.; Taboe, H. B.; Ngwa, G. A.; Ngonghala, C. N.

2026-07-07 infectious diseases 10.64898/2026.07.04.26355807 medRxiv
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Insecticide-treated bed nets (ITNs) are central to malaria control. They serve as physical barriers and chemical agents that deter and kill mosquitoes, thereby reducing transmission; however, this form of protection reshapes the immunology of malaria by reducing exposure to Plasmodium parasites and weakening the development of naturally acquired immunity. Against this background, the present study develops a modeling framework to investigate how this tension between protection and immunity alters malaria dynamics once vaccination is introduced as a complementary control strategy and the optimum combination of ITN and vaccine coverage required for malaria control. Unlike standard models that use a fixed proportional reduction in transmission, this study models ITN coverage and efficacy as coupled, time-dependent processes and immunity driven by exposure to infection and vaccination. Rigorous analysis of the model identifies existence conditions for equilibria and shows that malaria can be contained through the synergistic interaction of vaccination, vector control, and immunity-mediated host dynamics. Parameter values of the model are estimated by fitting the model to confirmed malaria case data and the estimated baseline reproduction number using these parameter values is 1.41 (95% confidence interval: 1.34-1.48), confirming sustained transmission. Simulations of the model show that, although ITNs reduce immunity acquisition, their net effect is to reduce infections and improve recovery and survival. Hence, population-level benefits of ITNs outweigh their immunity-reducing effects (particularly when combined with vaccination), leading to a reduced malaria burden. Comprehensive sensitivity analysis indicates that malaria burden is driven mostly by mosquito biting intensity, population capacity, and transmission probabilities; while mosquito mortality, effective treatment, ITN performance, and vaccine efficacy cause the most significant reductions. Additionally, malaria is uncontrollable with universal ITN use and vaccination at baseline efficacy. While individual interventions can achieve control under low transmission, neither 100% ITN coverage nor 100% vaccine coverage can achieve control under moderate-to-high transmission. However, a strong synergy between ITNs and vaccination allows combinations of high efficacy to achieve containment at realistic coverage levels, suggesting that integrated malaria control involving effective vector control, vaccination, and prompt treatment is needed.

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A Methodological Note on Empirical Confidence Intervals for the GCM-Ensemble Mean in Projecting Climate Change Impacts on Health

Tomo, Y.

2026-08-03 epidemiology 10.64898/2026.08.01.26359345 medRxiv
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In climate-health impact projection studies, projected impacts from multiple general circulation models (GCMs) are commonly aggregated by reporting the mean of GCM-specific impacts as the point estimate alongside a 95% empirical confidence interval (eCI) constructed from the 2.5th and 97.5th percentiles of the simulated pooled distribution of GCM-specific impacts. This study shows that the eCI generally does not yield the nominal coverage probability for the GCM-ensemble mean and constructs an interval aligned with the estimand. In a simulation study, the coverage of the eCI for the GCM-ensemble mean deviates from the nominal level in both directions, whereas the aligned interval yields coverage near 95% across all considered settings. The exact coverages derived analytically under a location-shift model agree with the simulation results. In a reanalysis of a heat-related mortality projection in London, the eCI is consistently wider. The eCI should be distinguished from confidence intervals for the GCM-ensemble mean; rather, the interval may be better described as a simulation-based approximate prediction interval for a GCM-specific impact under the uniformly randomly selected GCM from the considered GCM set.

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Dynamical Effects of Homologous Reinfections in a Multi-Strain Dengue Model

srivastav, A. K.; Steindorf, V.; Stollenwerk, N.; Kooi, B. W.; Aguiar, M.

2026-08-03 epidemiology 10.64898/2026.07.30.26359356 medRxiv
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Dengue transmission is shaped by multiple viral serotypes, temporary cross-immunity (TCI), antibody-dependent enhancement (ADE), and repeated exposure in endemic populations. Classical multi-strain models usually assume lifelong protection against reinfection with the same serotype. However, recent evidence suggests that homologous dengue reinfections, although rare, can occur. Their population-level consequences remain poorly understood. We extend a two-infection, two-strain dengue model with TCI and ADE-mediated transmission differences to include homologous reinfections. Homologous reinfection is represented by two exploratory parameters: relative susceptibility to reinfection with the same serotype and relative infectiousness during homologous reinfection. Using equilibrium analysis, bifurcation diagrams, simulations, and phase-space projections, we examine how these parameters affect dengue dynamics and interact with TCI duration and seasonal forcing under intermediate and long TCI durations, with and without seasonality. The extended model shows that qualitative dynamics characteristic of endemic dengue transmission are reproduced mainly when susceptibility to homologous reinfection is low, so that homologous reinfections remain rare but dynamically influential. Longer TCI broadens regions of complex oscillatory dynamics, while seasonality shifts the bifurcation structure and makes torus bifurcations a central route to complex behavior. Although backward bifurcation can occur when homologous susceptibility exceeds the biologically meaningful range, this result should be interpreted as a mathematical mechanism rather than a realistic dengue scenario. These results indicate that rare homologous reinfection pathways can influence long-term dengue dynamics when interacting with immune history, TCI, ADE-mediated transmission differences, and seasonal variation. Incorporating such pathways may improve understanding of recurrent outbreaks and irregular incidence patterns in highly exposed populations.

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Treatment-Structured Modeling of Tuberculosis Transmission with Threshold Dynamics, Stability Analysis and Implications for Disease Control

Nayeem, J.; Salek, M. A.; Biswas, M. H. A.; Kabir, M. H.

2026-07-30 epidemiology 10.64898/2026.07.28.26359108 medRxiv
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Background: Tuberculosis remains a persistent infectious disease whose control is complicated by latent infection, delayed treatment, incomplete recovery, reinfection, and continuing transmission from infectious individuals. Although treatment is central to tuberculosis management, it is frequently represented only as a transition parameter in mathematical models rather than as a separate epidemiological state. In this study, treatment was therefore incorporated explicitly as an independent compartment so that its influence on transmission, recovery, disease-induced mortality, and long-term disease persistence could be evaluated. Methods: A deterministic nonlinear compartmental model was formulated by dividing the total population into susceptible, exposed, actively infected, treated, and recovered classes. Reinfection of recovered individuals, progression from latent infection to active disease, movement of infectious individuals into treatment, treatment-associated recovery, natural mortality, and disease-induced mortality were included. Positivity and boundedness of the solutions were examined to establish biological validity. The basic reproduction number, R0, was derived through the next-generation matrix approach. Disease-free and endemic equilibria were determined, and their local and conditional global stability properties were investigated using Jacobian analysis, the Routh-Hurwitz criterion, center manifold theory, Lyapunov functions, and LaSalles invariance principle. Normalized sensitivity indices, Latin hypercube sampling, partial rank correlation coefficients, and numerical simulations were also applied. Results: The disease-free equilibrium was shown to be locally asymptotically stable when ,R0<1 whereas sustained transmission and a unique endemic equilibrium were associated with R0>1. Under the stated reduced-model assumptions, stability of the endemic equilibrium was established. Transmission-related parameters were identified as the strongest positive contributors to disease persistence. In contrast, treatment and recovery parameters were found to reduce the reproduction number and infectious burden. Numerical simulations indicated that stronger treatment implementation and reduced transmission opportunities produced substantial reductions in active tuberculosis cases. Conclusion: Treatment was shown to function as both a clinical pathway and an epidemiological control mechanism. The proposed framework may support the design of treatment-centered strategies for reducing tuberculosis prevalence and preventing long-term endemic persistence.

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Complexity of coupled behaviour-disease models and their relative performance against empirical data

Frimpong, S.; Bauch, C.

2026-07-27 epidemiology 10.64898/2026.07.23.26358796 medRxiv
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The initial response of populations to the SARS-CoV-2 virus reduced the incidence of COVID-19 cases. However, this success was shorted lived once most populations relaxed most restrictions, resulting in an increase in infections. This feedback contributed to additional pandemic waves. The temporal unfolding of behavioural changes in populations present a challenge to mathematical models for disease dynamics. Coupled behaviour-disease models with varying levels of complexity accounting for several factors have been used to capture behavioural dynamics and SARS-CoV-2 transmission, with varying results. To study the impact of model complexity on the predictive power of models, here we formulate five coupled behaviour-disease models with varying structure and number of parameters. We fit the models to SARS-CoV-2 infection incidence and stringency of control interventions from five European countries in the first wave, and study how well these fitted models predict the second wave. We show that models with more parameters do not necessarily have a greater ability to explain and predict key features of a pandemic wave. Hence, our results show that a relatively simple coupled behaviour-disease model with important parameters can do an adequate job of providing information about the pandemic wave. Additionally, our findings show that complex models can be country-specific, working better for some countries and poorly for others. We conclude that modellers should not always opt for the most complicated possible models, if the data do not support their use.

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Climate-Driven Malaria Transmission Dynamics with Human Awareness and Optimal Control: A Deterministic Mathematical Modeling Approach.

NYABWANGA, R. N.; Ketter, L. K.; Osogo, A. N.; Obogi, R. K.; Agasa, L. O.; MONARI, F. N.

2026-07-31 epidemiology 10.64898/2026.07.29.26359260 medRxiv
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Malaria is still one of the most dangerous causes of morbidity and mortality in tropical and subtropical regions even though it has been actively combated for many years. In 2023, there were approximately 263 million malaria cases and 597,000 deaths from this disease on a global scale, with sub-Saharan Africa being the region most affected by it [24]. Climate factors affect mosquito biology, including their abundance, survival, and biting rates, as well as parasite development, while human awareness plays a crucial role in adopting preventive measures and effective treatments. Despite the progress in both climate- and awareness-based malaria modelings, few studies integrate these factors in one comprehensive model that involves the detailed mechanisms of transmission processes. The current study develops a deterministic climate-driven SEAIR-SEI malaria transmission model that includes the impact of temperature, rainfall, and humidity on mosquito biology and endogenous community awareness. The model was proven to be well-posed by showing the positivity and boundedness of its solution and through the demonstration of the existence and uniqueness of its solution. The malaria-free equilibrium was determined, and the basic reproduction number was calculated using the next-generation matrix method. The model underwent local and global stability analyses to characterise the diseases persistence in the population. Additionally, a normalized forward sensitivity analysis was conducted, revealing the mosquito biting rate as the key force driving malaria transmission. Four time-dependent malaria interventions, namely, long-lasting insecticidal nets, community awareness campaigns, indoor residual spraying, and prompt treatment, were included in the model through optimal control theory and analysed using Pontryagins Maximum Principle. The numerical results for the optimal control problem showed that employing all four interventions leads to the best outcome by decreasing the objective functional value by 88.17%, reducing the total number of infected humans by 92.49%, and minimizing the total number of infectious mosquitoes by 93.87%. Interestingly, combining two interventions, indoor residual spraying, and prompt treatment, also yielded nearly optimal results. Therefore, the designed control strategy can serve as an efficient and affordable framework for malaria control in sub-Saharan Africa.

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Mathematical Modeling of Rift Valley Fever in the Sahelian Zone

Djimramadji, H.; Ndonane, B.; Djaouga, P.; MARKHOUS, H. M.; Djoumountanan, E.; TOBAYE, K.; Abakar, F. M.

2026-07-17 epidemiology 10.64898/2026.07.15.26358164 medRxiv
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We develop a mathematical model of Rift Valley Fever integrating mosquito vectors, ruminants, and humans, based on an SEIR-type structure with vertical transmission in vectors. Local data from the Sudanian and especially the Sahelian zones are used to capture the impact of climatic variations on mosquito population dynamics. The mathematical analysis establishes the models positivity, determines the basic reproduction number R0, and demonstrates the local and global stability of the disease-free equilibrium. Sensitivity analysis (PRCC) highlights the most influential parameters, while the stochastic approach using a continuous-time Markov chain confirms the major role of seasonal rainfall. Numerical simulations reveal a peak in animal and human infections around the 9th month, correlating with periods of heavy rainfall. This model provides a relevant tool for surveillance and prevention within a "One Health" approach in Chad.

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Prediction of brucellosis incidence in China's five highest-incidence provinces: Comparing time-series models with multi-source environmental predictors

QIN, Y.; Gao, Q.; Liu, H.; Fan, H.; Wang, Q.; Zhang, W.; Li, C.; Chen, Q.; Cui, Z.

2026-07-13 epidemiology 10.64898/2026.07.09.26357632 medRxiv
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Background Brucellosis is a severe zoonotic disease with pronounced seasonality and regional heterogeneity in high-incidence areas of China. Reliable forecasting tools are needed to inform prevention strategies, but the optimal modeling approach across different regions remains unclear. Principal Findings We collected monthly brucellosis incidence and 17 environmental variables from 2014 to 2024 across five high-incidence provinces: Inner Mongolia, Xinjiang, Shanxi, Heilongjiang, and Hebei. A three-step procedure--cross-correlation analysis, multicollinearity diagnostics, and stepwise regression--was used to select exogenous predictors. We then compared four time-series models: seasonal autoregressive integrated moving average (SARIMA), SARIMA with exogenous variables (SARIMAX), long short-term memory (LSTM), and LSTM with exogenous variables (LSTMX). All five provinces showed a unimodal seasonal pattern with peaks between April and July, though environmental drivers and optimal lag periods varied substantially by region, ranging from 1 to 6 months. In forecasting performance, LSTM achieved the highest accuracy in Shanxi (R2=0.925), Hebei (R2=0.876), and Xinjiang (R2=0.829), outperforming SARIMA and SARIMAX. LSTMX performed best in Inner Mongolia (R2=0.759) and Heilongjiang (R2=0.772) but showed weaker performance than LSTM in Shanxi and Hebei. Overall, adding exogenous variables did not consistently improve predictions across provinces. Conclusions Our findings demonstrate that LSTM-based models offer clear advantages for brucellosis forecasting in most high-incidence provinces, but the value of incorporating environmental predictors is region-dependent. These results support the development of tailored early warning systems and precision prevention strategies for brucellosis in high-risk areas of China.

10
Lessons learned from real-time nowcasting: The 2024 dengue outbreak in Puerto Rico

Tran, Q. M.; Detmar, A. M.; Liu, C. Y.; Madewell, Z. J.; Rodriguez, D. M.; Aponte, J. T.; Marzan-Rodriguez, M.; Paz-Bailey, G.; Adams, L.; Holcomb, K.; Johansson, M. A.; Thayer, M.

2026-07-22 public and global health 10.64898/2026.07.20.26358497 medRxiv
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Real-time nowcasting enhances situational awareness by mitigating reporting delays that obscure transmission dynamics. We applied Nowcasting by Bayesian Smoothing (NobBS) to the 2024 dengue outbreak in Puerto Rico (PR), using case surveillance data from the PR Department of Health. The method accurately captured the epidemic trajectory and consistently outperformed a baseline model, although reporting anomalies occasionally reduced performance. We also conducted analyses by dengue virus serotype and health region, as well as previous years. For analyses with few dengue cases, a model in which parameters are jointly estimated across groups generally achieved better performance than the independent one. Historical analyses revealed that years with higher variability in reporting delays generally exhibited higher uncertainty. The findings here underscore key lessons for real-time dengue nowcasting: alternative models may be needed in complex circumstances, but with stable reporting patterns and continuous evaluation, nowcasts can be a reliable and valuable public health tool.

11
Optimizing Wastewater Surveillance Sites for COVID-19 Hospitalization Forecasting Across U.S. States

Kaur, G.; Chen, J.; Adiga, A.; Adiga, A.; Espinoza, B.; Lewis, B.; Marathe, M.; Venkatramanan, S.; Warren, A.; Vullikanti, A.

2026-07-22 infectious diseases 10.64898/2026.07.20.26358167 medRxiv
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In this study, we analyze viral load data from wastewater treatment plants (WWTPs) across multiple U.S. states and address the challenge of selecting an optimal subset of sites to improve COVID-19 hospitalization forecasts. Using forward (greedy) regression with a baseline ARIMA model, we identify the most informative WWTPs that enhance forecast accuracy while reducing the number of sampling locations. Our analysis, based on NWSS data, shows that the optimal number of sites typically ranges from 2-8, though some states, including NY, IL, and WI, benefit from a larger set (10-20). We also leverage a Virginia-level digital twin model specifically designed for wastewater data modeling and analysis and our results show that for different parameter settings, that forecast accuracy can be achieved with strategically chosen small number of sites, providing

12
A mechanistic statistical model of dengue dynamics in an endemic region

Luna-Martinez, N.; Cruz-Rodriguez, E. X.; Bernal-Castro, E. A.

2026-09-03 epidemiology 10.64898/2026.09.01.26361961 medRxiv
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Background Dengue is a major public health challenge, and predictive models are crucial for early warning systems. However, many current modeling practices rely exclusively on climatic factors or employ complex algorithms that lack the interpretability needed for informed public health decision-making. To address these shortcomings, we developed and validated a multidimensional, interpretable statistical model to predict monthly dengue incidence. Methodology/Principal Findings We used a Generalized Linear Mixed Model (GLMM) with a Negative Binomial distribution to analyze 14 years (2010-2023) of spatiotemporal data from 37 municipalities in Huila, Colombia, an endemic region. The model integrates non-linear and lagged effects of climatic, demographic, and socioeconomic factors. The final model underwent rigorous external validation on an independent test set (2021-2023). Our model demonstrated high predictive discrimination (R2 = 0.743, Spearman's {rho} = 0.657), accurately capturing the timing of epidemic outbreaks. Key findings include the identification of an optimal thermal window for transmission at 27-28{degrees}C, a threshold effect for precipitation above 800 mm, and a saturation dynamic in outbreak autocorrelation. Conclusions/Significance This mechanistically-informed statistical approach provides a robust and transparent tool for epidemiological surveillance, successfully balancing high predictive performance with the explanatory power needed for effective, data-driven public health interventions.

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Evaluating the roles of weather and bird dynamics in accurately forecasting West Nile virus infection in mosquitoes and humans

Oshinubi, K.; Covington, J.; Busser, N.; Townsend, J.; Will, J.; Ruberto, I.; Kretschmer, M.; Chen, Y.; Doerry, E.; Hepp, C. M.; Mihaljevic, J. R.

2026-08-31 epidemiology 10.64898/2026.08.27.26361564 medRxiv
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Mosquito-borne diseases pose a growing public health challenge as climate change reshapes vector population dynamics. West Nile virus (WNV), transmitted between birds and Culex mosquitoes, disproportionately affects Maricopa County, Arizona, one of the nation's highest-burden counties, yet whether models that include weather and avian dynamics improve forecast accuracy remains unclear. Using a 15-year weekly time series of mosquito abundance, mosquito infection prevalence, and human cases, we developed four mechanistic model configurations of varying complexity, from mosquito-human dynamics alone to full models incorporating avian dynamics and weather forcing. We fitted each model to the weekly-observed data, generated probabilistic 1- and 2-week-ahead forecast horizons, and evaluated forecasts against a historical baseline. All configurations fit the data equally regardless of weather or avian dynamics. However, models incorporating both birds and weather created more accurate forecasts of mosquito abundance and mosquito infection prevalence, and all configurations outperformed the baseline for forecasting human cases. Forecast accuracy was highest in summer and fall, and ensemble aggregation sometimes outperformed every individual model, stabilizing predictions across the 15-year record. These findings indicate that avian and weather dynamics are most critical for predicting mosquito-specific data, positioning this framework as a scalable tool for public health planning for WNV surveillance under climate change.

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Mathematical Modeling of Japanese Encephalitis: Multi-Host Transmission Dynamics and Intervention Strategies

Devihosoor, M. C.; P., S. K.; V., S. P.; R., D. T.; Hiremath, J.; P., S. P.

2026-08-28 epidemiology 10.64898/2026.08.25.26361297 medRxiv
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Japanese encephalitis virus (JEV) transmission involves complex interactions among Culex mosquitoes, amplifying pig hosts, reservoir wading birds, humans, and environmental conditions, complicating quantitative assessment of transmission dynamics and intervention effectiveness. We developed a deterministic, fourteen-compartment One Health mathematical framework that integrates these interconnected host vector populations and their epidemiological states. The model incorporates temperature-dependent mosquito biting, seasonal transmission, human vaccination, pig biosecurity, environmental barriers, and mosquito-control interventions. Mathematical properties were established through analyses of non-negativity, boundedness, biologically feasible equilibria, local and global stability, and optimal control. District-specific simulations were conducted for Bellary, Udupi, Kolkata, and Purba Bardhaman during the August transmission period. Intervention scenarios were evaluated, and global sensitivity analysis was performed using 500 Latin hypercube samples with partial rank correlation coefficients. Model outputs were also compared with district-level surveillance observations. Vaccination-adjusted basic reproduction numbers were 0.905 in Bellary, 0.965 in Udupi, 1.817 in Kolkata, and 0.885 in Purba Bardhaman, with only Kolkata exceeding the epidemic threshold. Under maximum intervention, total infections decreased by 80.6%, 96.8%, 80.5%, and 72.2%, respectively, while infected mosquito populations declined to zero across all four settings. In Kolkata, vaccinating 3.6 million individuals with dose series II reduced the reproduction number from 1.817 to 0.9846, whereas population-wide dose series I vaccination alone was insufficient to reduce it below unity. Sensitivity analysis identified mosquito recruitment, temperature-dependent biting, carrying capacity, mosquito mortality, density-dependent regulation, and mosquito-to-human transmission as major determinants of peak human infection. Overall, the framework demonstrates heterogeneity in JEV transmission and intervention effectiveness and provides a mathematically grounded One Health approach for comparative evaluation of integrated control strategies.

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Multi-model forecasting of respiratory disease activity in Germany during the 2024-2025 season

Bracher, J.; Wolffram, D.; Amaral Lind, R.; Bardeck, N.; Boehm, M.; Contreras, S.; Doenges, P.; Guenther, F.; Kaiser, R.; van de Kassteele, J.; Kuhlmann, A.; Lange, B.; Nemcova, B.; Priesemann, V.; Reinacher, U.; Rodiah, I.; Sandmann, F.; the RESPINOW Study Group, ; Schienle, M.

2026-07-21 epidemiology 10.64898/2026.07.20.26358471 medRxiv
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Respiratory diseases cause considerable morbidity in autumn and winter and are a priority in public health monitoring. In Germany, they are subject to a number of surveillance systems, including both pathogen-specific and syndromic indicators. In this paper we present a collaborative multi-target and multi-model real-time forecasting system rolled out during the 2024/25 season, and discuss differences to earlier efforts carried out during the COVID-19 pandemic. A total of nine models were run to generate forecasts of general practitioner consultations for acute respiratory infections (ARI), hospitalizations for severe acute respiratory infections (SARI) and confirmed cases of seasonal influenza and RSV. As all indicators were subject to retrospective revisions, forecasting models were combined with a nowcasting step. Whenever multiple models were available for the same indicator, we combined them into an ensemble. Nowcasts showed convincing performance, even though for some models Christmas break effects led to an upward bias in early January. Forecasts were overall well-calibrated and most models outperformed simple benchmark models. These improvements were generally more substantial for age-stratified than pooled targets, and concentrated at lead times of two to three weeks. Anticipating the peak timing and magnitude proved to be challenging, with many models predicting too flat curves with a too early turnaround (e.g. already in late January rather than mid-February for SARI). The combined ensemble forecast was among the best-performing approaches, but unlike in previous related projects did not consistently outperform individual models. We conclude by discussing learnings on the organization of collaborative forecasting projects in post-COVID-19 times and the potential of AI-supported modelling.

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Quantifying the impact of bacterial vaccines against antibiotic resistance: accounting for transmission and selection dynamics

Aupepin, C.; Opatowski, L.; van Bommel, I.; Sieswerda, E.; Schweitzer, V.; Loisel, S.; TEMIME, L.; Leclerc, Q. J.

2026-08-28 epidemiology 10.64898/2026.08.25.26361172 medRxiv
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Vaccines, by reducing bacterial infection, transmission and/or colonisation, are promising investments against the global rise of antibiotic resistance (ABR). From a public health perspective, while efforts are put in developing bacterial vaccines, anticipating their potential impact on ABR is essential. We developed a compartmental model formalising inter-individual transmission and selection pressure through both bystander and targeted antibiotic exposure. Following a mathematical analysis of the model's equilibrium points, we explored the impact of different vaccines through simulations for two bacterial types. In simulations, vaccines consistently reduced infection incidence, although to varying extents. For S. aureus, a vaccine reducing acquisition rate, infection rate and colonisation duration by 60% at 70% coverage reduced total infections by 80%, while this reduction was only of 48% for E. coli. The impact on the resistance proportion among colonised differed markedly: this same vaccine increased it by 11% for S. aureus, while decreasing it by 8% for E. coli. Overall, our results highlight that population level impact on ABR strongly depends on the vaccine mechanism of action. The proposed model, which gathers the main drivers involved, provides a general framework that can be adapted to a wide range of bacterial pathogens and vaccines.

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A Mechanistic Framework for Modeling Insulin-Glucose-Glucagon Dynamics Under Malaria Co-Infection

Nyabadza, F.

2026-07-14 epidemiology 10.64898/2026.07.11.26357811 medRxiv
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Malaria and diabetes represent two globally significant metabolic disorders whose co-occurrence leads to complex, poorly understood pathophysiological interactions. Plasmodium infection disrupts glucose homeostasis through parasite-driven glucose consumption, inflammatory cytokine production, and pancreatic /{beta}-cell dysfunction, while diabetes impairs host immunity and increases malaria susceptibility. To date, no mathematical framework has captured the bidirectional coupling between these systems. Here we extend the insulin-glucose-glucagon (IGG) model of Dalton et al.\ (2026) by introducing a fourth state variable representing parasite load, incorporating malaria-induced insulin suppression, parasite-driven glucose consumption, inflammatory gluconeogenesis, bidirectional glucagon dysregulation, and insulin-dependent immune enhancement of parasite clearance. We establish positivity, boundedness, existence and uniqueness of steady states, local stability via Routh-Hurwitz criteria, global stability via Lyapunov functions, and sensitivity analysis of parameters driving hypoglycemia risk. Numerical simulations characterise the model across healthy, diabetic, and co-infected states. They show that parasite-driven glucose consumption and inflammatory gluconeogenesis act antagonistically on circulating glucose, that insulin-enhanced immunity lowers peak parasitemia through a saturating clearance term, and that increasing the half-life of exogenous insulin raises hypoglycemia risk in all host states. These mechanisms provide testable hypotheses for the clinical management of malaria-diabetes patients and identify potential therapeutic targets (TNF- blockade, glucagon analogues) for mitigating co-infection morbidity.

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Dynamics, Optimal Control, and Spillover Risk of the 2026 Bundibugyo Ebola Outbreak in the Democratic Republic of the Congo

Li, J.; Lai, S.; Su, Y.; Chen, Q.; Rui, J.; Zhao, Z.; Chen, T.

2026-08-18 public and global health 10.64898/2026.08.17.26360567 medRxiv
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In 2026, a Bundibugyo ebolavirus (BDBV) outbreak emerged in the Democratic Republic of the Congo (DRC), with 4,566 confirmed cases and 2,128 deaths reported as of 11 August, potentially becoming the largest Ebola outbreak on record globally. We developed a susceptible-exposed-infectious-deceased-recovered (SEIDR) model incorporating incorporating three categories of interventions, public self-protection, safe burial, and treatment and convalescence, to assess early transmission dynamics, the current epidemic trajectory, and cross-border spillover risk, and to inform the formulation of control strategies. Based on cumulative confirmed case data up to 31 July, sensitivity analyses across multiple candidate start dates identified 28 March as the optimal start date of sustained transmission, with 31 March to 3 April as the most likely onset window. As of 31 July, the basic reproduction number (R0) was 1.83 (95% CI: 1.81-1.84). When 58.12% of the susceptible population adopted protective behaviours, the transmission chain could be effectively interrupted. By integrating the non-dominated sorting genetic algorithm II (NSGA-II) with Pontryagin's minimum principle (PMP), we derived a time-varying optimal control strategy, with adjustments every two weeks, that could shorten the epidemic duration by approximately 7 months. Using International Migrant Stock data and Facebook IP-based mobility data with the Prophet forecasting model, we assessed spillover risk. Four countries were identified as very high risk at the end of July. Compared with the status quo scenario, the optimised control strategy could substantially reduce global importation risk. Enhanced entry screening and preparedness are warranted in neighbouring countries of the DRC in Africa, France in Europe, and Canada in North America.

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Rethinking respiratory disease forecasting: temporal heterogeneity between surveillance predictors and outcomes drives forecast instability

Topazian, H. M.; Sheets, T. R.; Gruninger, R. J.; Kelley, J.; LaCross, N.; Samore, M. H.; Lofgren, E.; Keegan, L. T.

2026-08-22 epidemiology 10.64898/2026.08.19.26360833 medRxiv
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Since the COVID-19 pandemic, forecasting hubs and non-traditional respiratory disease surveillance streams have become increasingly common. However, many forecasting approaches assume that relationships between surveillance predictors and disease outcomes remain stable over time and that incorporating additional historical data will improve forecast performance. To evaluate these assumptions in a real-world setting, we developed and evaluated forecasts of SARS-CoV-2 and influenza hospitalizations in Utah using syndromic surveillance, test positivity, and wastewater data. Rather than identifying a single, best-performing model, we examined whether relationships between surveillance predictors and hospitalization outcomes remained stable across seasons and whether longer historical training periods consistently improved forecast accuracy. Relationships between surveillance predictors and hospitalizations varied substantially by pathogen and season. Analyses using pooled data across multiple years suggested strong positive correlations between predictors and outcomes, but these aggregated patterns often obscured weak or negative correlations observed during SARS-CoV-2 variant waves and influenza seasons. Forecast performance similarly varied over time. Models that performed well during some seasons, transmission phases, or under certain training strategies frequently performed worse than benchmark models in others. Training on additional historical data generally reduced forecast accuracy, though this varied by disease and transmission phase. Forecasting groups should prioritize continual evaluation of surveillance predictors, adaptive strategies, and diverse ensembles, rather than relying on a single model, data stream, or historical training framework each year.

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Epidemiological methods provide target metrics and control parameters for multi-actor violent conflicts

Smah, M. L.; MacKay, N.

2026-08-10 epidemiology 10.64898/2026.08.05.26359787 medRxiv
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Violent conflicts increasingly involve multiple armed actors competing for influence over shared civilian populations, creating complex dynamics that challenge conventional security analysis and policy design. We present a framework that adapts epidemiological methods informed by the conflict landscape in Nigeria to model multi-actor violent conflict as an epidemic process. We derive a basic insecurity reproduction number ($R_0$), identify violence-free and persistent-violence equilibria, and introduce a novel Civilian Harm Index (CHI) to quantify humanitarian impact. Sensitivity analyses identify recruitment, ideological support from civilian populations, and abduction as the key drivers of conflict persistence and civilian harm. The framework reveals several counterintuitive findings. Interventions that most effectively suppress violence transmission are not necessarily those that minimise civilian harm, demonstrating that epidemic control and humanitarian protection may require distinct optimisation criteria. Likewise, interventions effective against one armed actor may be ineffective, or even counterproductive, when applied uniformly across groups. In addition, prisoner exchange and ransom payments increase violence persistence and civilian harm. Although developed as an illustrative rather than predictive framework, our results show that epidemiological methods provide quantitative metrics for evaluating intervention priorities and trade-offs in complex multi-actor conflicts.